VEGF-C, an indispensable growth factor for producing new neurons


The decline of the neurogenesis mechanism (production of new neurons) during ageing is implicated in the emergence of neurodegenerative diseases such as Alzheimer’s disease. Research studies bringing together Inserm, CNRS and Université de Pierre et Marie Curie researchers from the Brain and Spinal Cord Institute (Inserm/ CNRS / Pierre and Marie Curie University), in collaboration with a team from the Yale Cardiovascular Research Center, have demonstrated the importance of factor VEGF-C in the activation of neural stem cells, and hence in the production of new neurons. These results, published in Cell Reports, bring fresh hope for the development of therapies that may help to improve the production of neurons to alleviate cognitive decline in people with Alzheimer’s disease.

Throughout life, adults are able to generate new neurons from neural stem cells (NSC), in order to maintain their complement of cognitive skills. This neurogenesis occurs in the hippocampus, a brain structure that plays a central role in memory. However, age and some strokes lead to a decline in this function, and can contribute to the appearance of serious cognitive disorders, such as Alzheimer’s disease.

Although the stages in the formation of new neurons are well known, the molecular mechanisms of this phenomenon are less well understood. Indeed, NSC spend most of the time in a quiescent state during which the cells are outside the cell cycle and do not divide. The repressors that maintain this quiescent phase have been identified, but there are still many questions about the factors that make it possible to exit this cell “dormancy.”

Against this background, Jean-Léon Thomas and Anne Eichmann decided to focus on the vascular endothelium growth factors (VEGF) and their receptors (VEGFR), which are already suspected of involvement in regulating the growth and maintenance of nerve cells. More specifically, they chose to study the potential activating ability of factor VEGF-C when bound to its receptor, VEGFR3.

Their in vitro and in vivo experiments confirm that rodent NSC possess receptor VEGFR3 and also produce factor VEGF-C. Stimulation of NSC by VEGF-C leads to the activation of these cells, i.e. their entry into the cell cycle and conversion into neural progenitor cells, and ultimately, the production of new neurons. The specific feature of VEGF-C action in the brain, compared with other vascular growth factors such as VEGF-A, is that it induces the NSC to respond at concentrations that do not induce vascular proliferation. This property confers potential interest on VEGF-C as a specific activator of NSC in the brain.Photo2©Inserm, Jinah Han. Among the hippocampal neural stem cells (characterised by expression of Nestin [in white] and GFAP [in red]), those that possess receptor VEGFR3 (in green) are very numerous.

In mice that produce VEGFR3-deficient NSC, this neurogenesis phenomenon is abolished. The scientists thus show that VEGF-C/VEGFR3 signalling is not just involved, but is absolutely required for the neural stem cells to “awaken,” and is hence required for the creation of new neurons.

This mutant model also enabled the team to observe a correlation between mood disorders and deterioration of the neurogenesis function of the hippocampus. As suspected, these mice, in which NSC activation is compromised, develop exaggerated anxiety on ageing, similar to that seen in patients with Alzheimer’s disease. This result suggests that VEGF-C/VEGFR3 neural signalling participates in the maintenance of cognitive functions in the murine model.

Observations validated in humans

As a logical continuation of this work in rodents, the researchers wondered about the presence of similar mechanisms in humans. They then discovered that this signalling pathway is conserved in human nerve cells, where it also promotes cell proliferation and survival in vitro.

Although these results are still preliminary, they provide arguments to support the idea that adult NSC activity could have a central role in physiological and behavioural control in the body. Similarly, the decline in this activity during ageing could be associated with the onset of mood disorders such as anxiety and depression.

From the therapeutic point of view, these studies are encouraging: VEGF-C might be a good candidate for improving the production of new neurons and offsetting cognitive decline in people with Alzheimer’s disease.

European Patent Office rankings for 2014: Inserm 6th in France for patent applications, 1st in Europe for patent applications in biomedical research

Inserm, with the help of its subsidiary Inserm Transfert, continues to rise in the 2014 rankings of French patent applicants issued by the European Patent Office (EPO). Inserm is placed 6th in France (among applicants in all organisations and sectors combined), 4th in Europe for the “Biotechnology” sector and 5th in Europe for the “Pharmaceuticals” sector[1].

Again, according to the 2014 rankings of the European Patent Office, 227 patent applications were filed in Inserm’s name, strengthening its position compared with previous years as the leading academic organisation for biomedical research in Europe. On the French scale, Inserm has moved up five places compared with the EPO 2012 rankings (11th place in 2012, 6th this year).

“This ranking reflects a strategy of innovative research, the protection of which is one of the key elements favouring its transfer to industry for the benefit of patients and society,” claims Yves Lévy, CEO of Inserm.

At present, Inserm has a patent portfolio of 1,279 patent families (+102% since 2006). Inserm Transfert, which is in charge of Inserm’s intellectual property strategy, and of the management and commercialisation of the portfolio, wrote and submitted over 50% of patent applications in 2014, and licensed 26.5% of the portfolio to industrial partners in France and around the world (large health industry groups, intermediate, small and medium enterprises and start-up companies).

“Inserm’s highly diversified portfolio, which covers the major disease categories, with applications in diagnostics and therapeutic development, constitutes a pool of opportunities for industrial partners at the early stages of innovation. This substantially explains Inserm’s current position in the EPO rankings,” comments Pascale Augé, CEO of Inserm Transfert.

About Inserm –

Inserm, the French National Institute of Health and Medical Research, has been, since 1964, the only public body in France dedicated to biological and medical research and human health, with nearly 13,000 researchers, engineers and technicians, and some 300 research laboratories. The Institute is to be found throughout the pathway from research laboratory to the patient’s bedside, and carries out research in a variety of areas, making it possible to study all diseases, from the commonest to the most rare. Inserm is a founding member of Aviesan, the French National Alliance for Life Sciences and Health, created in 2009.
* Other founding members of Aviesan: CEA, CNRS, CHRU, CPU, INRA, INRIA, Institut Pasteur, IRD

About Inserm Transfert –

A private subsidiary of Inserm founded in 2000, Inserm Transfert SA manages all commercialisation and transfer of knowledge from Inserm laboratories to Industry, from invention disclosure to industrial partnership. Inserm Transfert also offers services related to setting up and managing European and international projects, and large-scale projects in epidemiology and public health. It manages a budget of €2 million for proof of concept. Finally, Inserm Transfert also supports entrepreneurs in the biotechnology sector, in partnership with Inserm Transfert Initiative, a venture capital company with a capital of €39.7 million to support the life sciences.

[1] Sources:; Press conference: click here; Annual report: click here 

Saturday 28 February: World rare disease day

A disease is said to be rare if it affects fewer than 1 in 2,000 people, or, for France, fewer than 30,000 people for a given disease. Rare diseases are highly diverse, are found in all areas of medicine, and are often serious, chronic, and progressive.

These diseases, also known as “orphan diseases,” affect approximately 3 million people in France, and between 27 and 36 million people in Europe.[1]

The theme chosen for this 8th World Rare Disease Day, “Living with a Rare Disease – Day-by-day, hand-in-hand!” pays tribute to the patients, families, carers and researchers who deal with rare diseases on a year-round basis.

Orphanet, a portal hosted by Inserm, provides free and open access to all the information on rare diseases and orphan drugs, validated by experts and continuously updated. It is thus possible to search for a rare disease among the 8,000 referenced in the database, and see a description of it and the related resources. Already available as a mobile application, compatible with iPhone or iPad, this year Orphanet is launching Orpha Guides, an application focused on providing information about the disability associated with a rare disease, and the assistance and benefits available to patients.

To find out more, visit

OrphaNews: the Rare Disease community newsletter

The French Foundation for Rare Diseases, of which Inserm is a founding member, brings together players in research and in care (from the public, private and non-profit sectors), in order to encourage research in all areas for the benefit of patients.

To find out more, visit

[1] Source : Fondation for Rare Diseases

Preliminary results of the JIKI clinical trial to test the efficacy of favipiravir in reducing mortality in individuals infected by Ebola virus in Guinea.

Preliminary data from the JIKI clinical trial, which is testing the efficacy of favipiravir[1] in reducing mortality associated with Ebola, provide two important pieces of information:

• absence of efficacy in individuals who arrive at treatment centres with a very high level of viral replication and who already have serious visceral involvement,

• and encouraging signs of efficacy in individuals arriving at treatment centres with a high or moderate level of viral replication, who have not yet developed overly severe visceral lesions.

With this classification into two groups, we have a much better understanding of Ebola virus disease, and can redefine the role of antiviral monotherapies in the therapeutic arsenal used against the disease.

The trial, sponsored by Inserm and funded by the European Commission from the Horizon 2020 Initiative under the project title REACTION, is supported by two NGOs, Médecins Sans Frontières/Doctors Without Borders (MSF) and Alliance for International Medical Action (ALIMA); two laboratory networks, Belgian First Aid and Support Team (B-FAST) and European Mobile Laboratory (EMLab); the French Red Cross, and the French Military Health Service.

These preliminary data are being presented on Wednesday 25 February as a late-breaking abstract at the CROI international conference (Conference on Retroviruses and Opportunistic Infections) in Seattle.

Essai clinique JIKI Inserm – Ebola treatment centre in Guékédou Guinea © X Anglaret & D Sissoko /Inserm

Given the high mortality associated with Ebola virus despite high-quality symptomatic treatment, study of specific innovative therapeutic agents is essential. Potentially useful drugs against the virus include favipiravir (T-705), an antiviral drug already tested against influenza virus in adult humans (and well tolerated). The latter (no more than other potential treatments) has never been tested in humans for treating Ebola, but its efficacy has been demonstrated in vitro and in mice.

As part of the mission given to Aviesan to organise the research as a matter of urgency, the JIKI clinical trial, a phase II multicentre noncomparative trial, began in Guinea on 17 December 2014, to test the ability of favipiravir to reduce mortality in individuals infected by Ebola virus.

Sponsored by Inserm, and jointly funded by the European Commission, the JIKI trial is being conducted in partnership with MSF, ALIMA, the French Red Cross, EMLab, B-Fast and the French Military Health Service, and is taking place in four Ebola treatment centres in Guékédou (MSF), Nzérékoré (ALIMA), Macenta (French Red Cross) and Conakry (carers’ treatment centre).

In these centres, adults and children over one year of age with a positive Ebola PCR test who agree to take part (parental consent in the case of minors) receive treatment with favipiravir for 10 days along with basic care. Favipiravir is provided by FUJIFILM Corporation/Toyama Chemical Co., Ltd. Favipiravir comes in the form of 200 mg tablets (the tablets can be dissolved in a drink) and is administered according to the following dose regimen :

– Adults: Day 0: 2,400 mg at H0, 2,400 mg at H8 and 1,200 mg at H16, then 1,200 mg twice a day for 9 days;

– Children: doses adjusted to body weight.

The JIKI trial is being followed by an independent monitoring committee, which met on 11 December 2014, and on 5 January, 14 January and 26 January 2015. At this last meeting, the committee authorised the investigators to publish the interim data, which they judged to contain messages that should be quickly shared with the international community. These messages, obtained from the first 80 participants (69 adolescents or adults, and 11 children) are as follows:

– 42% of participants arrived at the treatment centres with a strongly positive PCR test (cycle threshold value, CT, < 20), reflecting a very high viral load . Of these patients, 81% had refractory renal failure and 93% died. In the three months preceding the trial, mortality among individuals presenting with the same features was 85%. Comparison of the trial and pretrial data shows that it is highly unlikely that favipiravir monotherapy will ultimately be proven to reduce mortality in this population with advanced disease.

– 58% of participants arrived in the treatment centres with a cycle threshold (CT) ≥ 20, reflecting a high or moderate viral load. Of these patients, 42% had renal failure, but only 15% died. In the three months preceding the trial, mortality among individuals presenting with a CT ≥ 20 was 30%. Comparison of the trial and pretrial data therefore leads us to hope that favipiravir monotherapy may reduce mortality in this population with less advanced disease.

For the researchers, these preliminary data encourage us:

– to continue the trial while trying to provide favipiravir treatment as soon as possible after the symptoms appear, so as to treat patients in whom viral multiplication can be controlled, and who have not yet developed visceral lesions (especially renal lesions);

– to explore other therapeutic options for patients who come to the treatment centres when their disease is too far advanced.

Yves Levy, the chairman and CEO of Inserm said: “The results of this non-comparative trial have to be confirmed using a larger number of patients. However, they open up other therapeutic opportunities in drug combinations, in particular for the treatment of patients suffering from more advanced stages of this disease. They also clearly show that research plays an essential role in tackling such epidemics. I would also like to stress that without the excellent Guinean-French cooperation, the pioneering role of the Médecins Sans Frontières (MSF) in this research, the fruitful partnerships with all NGOs involved, and the European Commission’s responsiveness, this progress could not have been accomplished.”

European Commissioner for Research, Science and Innovation Carlos Moedas said: “I am excited about the encouraging results of one of our EU-funded projects to tackle Ebola. We have preliminary evidence that the antiviral drug ‘favipiravir’ may be effective against early Ebola disease. If these results are confirmed by the ongoing clinical trial, it will be the first-ever treatment to be deployed against this deadly disease during the current outbreak. These results show the success of the European Commission’s quick reaction to the Ebola outbreak to support urgent research on several potential treatments and vaccines against Ebola with funding from our Horizon 2020 research programme. This is an astounding example of what the best brains can achieve with EU support when there is so much at stake. It shows how EU funding can lead to discoveries that save people’s lives and which are the result of rapid EU, international and industry cooperation.”

According to Agustin Augier, Secretary-General of Alima, “Those positive results will reinforce the confidence between affected populations and the treatment center. This therapeutic solution, even if partial, will significatively attract ebola patients to the treatment center. It is a significative step towards tackling the outbreak in the villages where it still goes on.”

“MSF is pleased to see that favipiravir seems to have a positive effect for certain patients suffering from EVD. But it also seems that the most vulnerable patients, the people that are most likely to die from the disease, don’t benefit at all from favipiravir. That fact, and the fact that these are only preliminary results, show that it is really too soon to start using favipiravir outside a trial environment. Research into favipiravir, and into other potential treatments for EVD, must be continued, and MSF is willing to play a role in these clinical trials,” says Dr. Bertrand Draguez, medical director of MSF.

[1] “Favipiravir is provided by FUJIFILM Corporation/Toyama Chemical Co., Ltd.”

This project has received funding from the European Union’s Horizon 2020 research and innovation programme


Influenza: more than two million French affect

According to the weekly bulletin of the Sentinelles network, the incidence of influenza is close to its peak. In 5 weeks, 2 044 000 persons had consulted their doctor. The rates of incidence has been estimated that 231 cases per 100,000 inhabitants. A figure that exceeds the epidemic threshold (179 cases per 100,000 inhabitants).

At regional level, the highest rates of incidence were found in: Limousin, Provence-
Alpes-Côte-d’Azur and Midi-Pyrénées.

The study presently has 6 240 participants registered on the website. This research project, established by the Sentinelles network (Inserm – UPMC) and the French Institute for Public Health Surveillance, enables everyone to participate in influenza surveillance and research in metropolitan France, anonymously, voluntarily and directly online.

Additional data on influenza-like illness measured in the general population and the Sentinelles network’s Bulletin of 21/01/15 are available at

carte grippe 22012015

Severe asthma: gallopamil confirmed as a therapeutic approach

A team of Inserm researchers from the Cardio-Thoracic Research Centre of Bordeaux (Inserm/University of Bordeaux and Bordeaux University Hospital) has demonstrated the clinical efficacy of gallopamil in 31 patients with severe asthma. This chronic disease is characterised by remodelling of the bronchi, which exacerbates the obstruction of the airways already seen in “classic” asthma. In contrast to the reference treatment, gallopamil has proved capable of reducing the bronchial smooth muscle mass. This work is published in the 29 January 2015 issue of the American Journal of Respiratory and Critical Care Medicine.

Severe asthma is a chronic condition of the airways that affects between 1 and 3% of the world population to a highly variable extent, depending on the country. It is characterised by persistent breathing difficulty, restricted physical activity, frequent nocturnal attacks, and prolonged asthma attacks that require systemic treatment[1]. These symptoms lead to a considerable number of emergency hospital admissions, have a serious impact on the quality of life for patients, and can even result in death.

In severe asthma, bronchial obstruction causes a strong reduction in respiratory capacity. This bronchial obstruction is due to remodelling of the airways, particularly the thickening of the bronchial smooth muscle (BSM) that surrounds them. This phenomenon is associated with a poor prognosis and resistance to even intensive treatment. Until now, no pharmaceutical drug has succeeded in preventing the excessive proliferation of these muscle cells, including corticosteroids, the reference treatment for severe asthma.

In previous work, Patrick Berger and his colleagues had already demonstrated in vitro and ex vivo that this disproportionate growth was triggered by an abnormal entry of calcium into these bronchial smooth muscle cells[2]. In this same article, the scientists had demonstrated in vitro the anti-proliferative effect of gallopamil, which is normally prescribed for certain heart conditions because of its blocking action on calcium channels.

© Inserm, Pelletier L. The left pictures show the characteristic look  of lung inflammation in asthma with thickening of the bronchial wall, a lot of inflammatory cells and an abnormal production of mucus. Mice treated with the calcium channel inhibitor (on the right) are completely protected.

To assess its in vivo efficacy, the researchers then initiated a clinical trial sponsored by Bordeaux University Hospital and supported by the French Ministry and Health and Inserm. For 12 months, they thus measured the effect of the drug on the thickness of the BSM and bronchial wall, and the frequency of asthma attacks in 31 patients.

On analysis, the data showed a significant reduction in BSM in asthmatic patients treated with gallopamil compared with the placebo group. The drug therefore enabled a significant reduction in the thickness of the bronchial wall in patients.

After this phase, both patient groups were monitored for 3 months after stopping treatment. It then became apparent that individuals treated with gallopamil had significantly fewer prolonged attacks than the placebo group.

This pilot study thus provides proof of concept that the calcium channel blocker is able to reduce bronchial remodelling through its action on the smooth muscle cells in individuals suffering from severe asthma.

 Other studies involving larger patient cohorts will have to be put in place to confirm these results. Moreover, although gallopamil seems to affect the occurrence of prolonged asthma attacks, Patrick Berger emphasises the need to test gallopamil over a longer treatment period in order to confirm this observation.

[1] The episodes are also medically referred to as exacerbations.

[2] Berger P. et al., Bronchial smooth muscle remodeling involves calcium-dependent enhanced mitochondrial biogenesis in asthma. J Exp Med 2007; 204:3173-3181


FameLab: the scientific communication competition returns to France !

For the second consecutive year, FameLab, the international scientific communication competition organised by the British Council and its partners, is coming back to France !

Who is this competition for?

Whether you are a young researcher, student or teacher of science, FameLab invites you to present your chosen subject for three minutes to a panel of professionals from the communications, research and media sectors.

Three criteria need to be met: content, clarity and charisma!

How do you take part?

Heats will take place throughout France between March and April 2015 in partnership with scientific cultural organisations:
Brest, Océanopolis, Friday 6 March 2015 (closing date for entries 28 February 2015);
Marseille, Campus Saint-Charles, Tuesday 10 March 2015 (closing date for entries 3 March 2015);
Toulouse, Bazacle, Thursday 26 March 2015 (closing date for entries 13 March 2015);
Villeneuve d’Ascq, Forum des Sciences, Saturday 4 April 2015 (closing date for entries 4 March 2015);
Bordeaux, Cap Sciences, Friday 10 April 2015 (closing date for entries 10 March 2015);
Paris, venue and date to be announced in February

The national final will take place on 21 May in Paris.

Unavailable for the regional heats? You can submit a video entry.

Participation in FameLab also means:

An opportunity for the participants:
– to interact with other science enthusiasts and enjoy networking with FameLab candidates from France and around the world;
– to benefit from the informed opinions of recognised specialists;
– to publicly present the results of research, and share their passion for science.

Winners will receive:
– A two-day Masterclass at CERN (European Organization for Nuclear Research) in Geneva in order to refine their oral presentation technique and communication skills;
– For the national winner, the opportunity to take part in the international Grand Final at the Cheltenham Science Festival in the UK.

PhotoCP web

Further information:

All information on the competition and registration is available on the British Council website.

For any other questions: rf.licnuochsitirb@balemaf

This competition is organised in partnership with Inserm, the French National Centre for Space Studies (CNES), the French Association of Museums and Centres for the Development of Scientific, Technical and Industrial Culture (AMSCTI), the European Organization for Nuclear Research (CERN), the French Alternative Energies and Atomic Energy Commission (CEA) and the French Research Institute for Exploitation of the Sea (Ifremer).

Foetal growth restriction (FGR): assessment and impact of screening

An observational study carried out in France by Jennifer Zeitlin and her team (Inserm Unit 1153, Obstetrical, Perinatal, and Pediatric Epidemiology Research Team, EPOPé), on over 14,000 women, shows that only 21% of infants with foetal growth restriction (FGR) had been suspected of having FGR during pregnancy, despite national recommendations that invite women to have an ultrasound scan during the third trimester of pregnancy. The study shows that nearly half of the infants with suspected FGR were of normal weight at birth (false positives). Moreover, suspected FGR during pregnancy was associated with an increased risk of planned pre-labour caesarean delivery or induced labour, independent of the existence or otherwise of low birthweight. The results of this study, published in BJOG: An International Journal of Obstetrics and Gynaecology, emphasise the need to reflect on the reasons for the poor performance of FGR screening, and also raise questions about the potential iatrogenic effects of screening on the false positives.

© Fotolia

Foetal growth restriction (FGR) is an obstetric pathology that causes considerable perinatal morbidity and death. It appears as a change in foetal growth that can be detected during pregnancy, mainly by estimating foetal weight from ultrasound measurements. In France, the third trimester ultrasound recommended for all pregnant women serves to monitor foetal growth and identify foetuses with FGR. Antenatal detection of FGR enables monitoring of the pregnancy to be adapted to prevent risks of foetal and neonatal death, as well as risks of neurological sequelae for the infant.

Few studies to date had assessed the performance and impact of FGR screening on the general population. The aim of the researchers was to estimate the percentage of infants for whom FGR had been suspected antenatally, and to measure the effect of this suspicion on medical decision-making, by analysing a representative sample of births in France in 2010. To do this, they estimated the number of low birthweight (below the 10th percentile for gestational age) infants born and, of these, the proportion of infants who had been suspected of having FGR antenatally.

The study showed that only 21% of low birthweight infants had been suspected of having FGR during pregnancy. Furthermore, half of the infants suspected of having FGR during pregnancy were of normal birthweight (≥ 10th percentile). Antenatal suspicion of FGR was associated with an increased probability of having a planned pre-labour caesarean delivery or an induced labour, independent of the existence or otherwise of low birthweight. Similar results were obtained for the subgroup of women who showed no complications during pregnancy.

For Jennifer Zeitlin and her team:

“The results of this study emphasise the need for a reflection on the reasons for the poor performance of FGR screening in France. They also raise questions about risks from carrying out unnecessary medical interventions, where suspected FGR during pregnancy has not been confirmed at birth.”

Immune cells commit suicide to prevent allergy

Scientists from the CNRS, INSERM and Université de Limoges, working in the Laboratoire Contrôle de la Réponse Immune B et Lymphoproliférations (CNRS/Université de Limoges)[1] have demonstrated that the production of type E immunoglobulins (IgE)[2]by B lymphocytes induces a loss in their mobility and the initiation of cell death mechanisms. These antibodies, present in small quantities, are the most powerful “weapons” in the immune system and can trigger extremely violent immune reactions or immediate allergies (asthma, urticaria, allergic shock) as soon as their levels rise, even slightly. These findings, published online in Cell reports on 12 February 2015, thus elucidate how our bodies restrict the production of IgE in order to prevent an allergic reaction.


B lymphocytes under a confocal microscope (x1000). The cytoskeleton (actin molecules is labeled with a green fluorescent probe (phalloidin FITC). B lymphocytes with an IgM on their surface display protuberances (pseudopods) which testify to their mobility, while IgE+ B lymphocytes lose theses structures and become immobile.
© CNRS Laboratoire Contrôle de la réponse immune B et lymphoproliférations 

Immunity is based on cells, B lymphocytes, which carry or secrete antibacterial or antiviral “weapons”, the immunoglobulins (IgG, IgM, IgA, IgE) or antibodies. Although these weapons of immunity offer protection, they can also sometimes turn on us. This is the case for the most effective of antibodies, IgE, where even infinitesimal traces (these IgE are 100,000 times less abundant than other antibodies) can trigger extremely violent allergic reactions.

The lymphocytes that produce IgM, IgG or IgA are numerous, easily identifiable and persistent (as “memory cells”). For hitherto unexplained reasons, the cells that produce IgE are rare and have thus been the subject of very little study. In order to understand the mechanisms controlling IgE, the scientists first of all used genetic engineering to force cells to produce these antibodies in large numbers. They then succeeded in demonstrating two principal control mechanisms. They showed that as soon as a B lymphocyte carries an IgE on its membrane, it “freezes”, swells, loses its pseudopods[3] and becomes incapable of moving, although lymphocytes are generally highly mobile. The scientists also revealed that the lymphocyte activates several mechanisms leading to apoptosis, or programed cell death. This self-destruction causes the rapid elimination of lymphocytes carrying IgE, while other cells in the immune system are able to survive for up to several years.

During evolution, our bodies have thus developed several self-restriction mechanisms around one of their most powerful immune “weapons”, IgE. Because a cell carrying IgE can no longer move, it can only survive for a brief period — just long enough to play a short-lived protective role against parasites, toxins and poisons. It then self-destructs by committing a sort of “hara-kiri” which strongly reduces IgE production and hence the triggering of allergies. The scientists now wish to explore in more detail the different molecular pathways governing this self-restriction. Indeed, these may constitute numerous new therapeutic targets whose pharmacological activation could block allergies, or even permit the reduction of other pathological B lymphocytes, such as those involved in lymphomas.


Internalization of membrane IgE (spontaneous endocytosis) contributing to weak IgE expression and the death of these cells. Visualization under a confocal microscope (x1000) of IgE+ B lymphocytes at 37 °C with anti-IgE antibodies. This labeling is able to demonstrate the internalization of membrane IgE indicated in blue (right). 
© CNRS Contrôle de la réponse immune B et lymphoproliférations

[1] In collaboration with an immunologist from the Laboratoire Microenvironnement et Cancer (INSERM/Université de Rennes 1).
[2] Immunoglobulins, or antibodies, are proteins secreted by type B lymphocytes in reaction to introduction into an organism of a foreign substance (antigen).
[3]  Deformations of the membrane that allow a cell to eat and “crawl”.

Tous Chercheurs: Experiencing science in order to better understand their disease

Since 2004, the ‘Tous Chercheurs’ association, presided over by neurobiologist Constance Hammond (Director of Research of Inserm Unit 901 “Mediterranean Institute of Neurobiology (INMED)”), is offering a novel experience to members of patient groups.

This organisation arranges an average of seven practical training courses in biology per year, each one lasting three days, for people affected by chronic diseases (rare genetic diseases, autoimmune diseases, inflammatory diseases, familial cancers, …).  The details of this programme have just been published in the journal PloS Biology dated 10 February.


© Tous Chercheurs/M. Mathieu

These courses enable participants to learn, through practice, the fundamentals of biology necessary to understand their disease; to understand certain known (or supposed) mechanisms at the cause of the disease; and to gain awareness of the specifics and constraints of the research.

The groups are composed of 8 to 12 people, members of the same patient group or of groups affected by similar conditions.

Each session takes place at the Tous Chercheurs laboratory, based at the Mediterranean Institute of Neurobiology (INMED, Inserm), on the Luminy Science Campus (University of the Mediterranean).

Each session runs over three periods:

  • The first morning consists of an initial observation period, followed by questioning, which leads to the formulation of a theory of work. This first morning puts the trainee “in the shoes of a researcher” and into an active apprenticeship;
  • From the afternoon of the first day to the end of the third morning trainees carry out practical experiments linked to their disease;
  • The afternoon of the last day is dedicated to a meeting with a doctor or researcher working on their disease to discuss the latest advances in terms of research or treatment of the disease.

In 10 years, Tous Chercheurs has devised and presented 64 training sessions and as such has trained around 600 members of patient groups.

The prospect for the coming years is to extend this training to other Inserm laboratories. For now, Tous Chercheurs is coordinating training within the French Federation of DNA Schools including four other patient training centres (Angers, Evry-Généthon, Nîmes, Poitiers).

Among the associations welcomed (and associated diseases), we should note AFM (French Muscular Dystrophy Association – neuromuscular diseases), VLM (Cystic Fibrosis), APTEPF (familial polyposis), AFSR (Rett syndrome), AFAF (Friedreich ataxia), ASL (hereditary spastic paraplegia), Wegener (GPA) and other vasculitis updates, AFA (Crohn’s disease and ulcerative colitis), ANDAR (rheumatoid arthritis), AFPCA (relapsing polychondritis), AFDIAG (coeliac disease).

Some of the feedback from trainees who have participated in sessions:

“These three intense, interesting and engaging days have left us “truly wrecked”!  We have gone home very contented and only ask for one thing: to go back, revise, go into depth and still with the same aim: understand better to fight back more!  Thank you for what you do, thanks for the autoimmune patient groups and thanks for the patients.

Gilbert – French Association for Relapsing Polychondritis

“A very high level course which aimed at bringing it within reach of everyone and from which the full facts of knowledge, hope and desire to live can be retrieved in order to await achievements in research. “

Michel – Waldenstrom Association France

This was made possible thanks to the support of our funding partners, specifically: AFM-Téléthon, Courtin Arthritis Foundation , the PACA (Provence – Alpes – Côte d’Azur) Region , MENESR (French Ministry of National and Higher Education and Research, the town of Marseille, Inserm and Aix-Marseille University.