A microbiota bacterium protects the large intestine from inflammation

The microbiota, which is the term used to describe all micro-organisms living in the mucous membranes, is vital for our health and affects our development, metabolism, immune system etc. However, most of the mechanisms which allow it to play this important role have yet to be discovered. Researchers in Inserm Unit 892 “Nantes-Angers regional cancer research centre” have recently identified one of the mechanisms by which the microbiota enables our immune system to prevent inflammation of the large intestine. Their findings will be published on the Plos Biology website on 9 April.

The researchers identified a population of regulatory T cells hitherto undiscovered in humans – named DP8a – and demonstrated that an intestinal microbiota bacterium known as Faecalibacterium prausnitzii prompts their development.

Previous studies have revealed that this bacterium occurs in unusually low numbers in the faecal flora of patients suffering from inflammatory diseases of the digestive tract.
The researchers demonstrated in this study that the prevalence of DP8a lymphocytes specific to this bacterium is also lower in these patients, both in the mucous colic and the blood.

“The results show that this population of lymphocytes plays an important role in protecting the large intestine from inflammation. We have identified for the first time a mechanism in humans by which a microbiota bacterium contributes to the equilibrium of the mucous membrane it inhabits” explains Francine Jotereau, emeritus professor in the Inserm unit and co-author of this work.

These findings pave the way for developing markers and innovative therapies for preventing and treating inflammatory diseases of the digestive tract by restoring the anti-inflammatory activity of DP8a Treg cells in patients.

“These findings will also allow us not only to research the role of these regulatory T cells in controlling other conditions such as allergies or chronic infectious diseases but also to better understand the impact of the microbiota on the immune system” concludes Francine Jotereau.

Europe supports stem cell research for the treatment of diabetes

A €6 million grant awarded to the HumEn project by the European Commission has helped bring together the main institutes carrying out stem cell research, including Inserm, and European industrial partners wishing to develop insulin-producing cells as a future cell replacement therapy for diabetes.

The complete maturation of human pluripotent stem cells into transplantable beta cells* that may cure diabetes has not yet been achieved in the laboratory.

The objective of the HumEn project is to develop functional insulin-producing beta cells, which are lacking in people with diabetes,* from pluripotent stem cells. The advantage of pluripotent stem cells as a source of beta cells is that, in theory, they represent an unlimited source of insulin-producing cells.

The HumEn project, funded by the European Commission and coordinated by the University of Copenhagen, brings together six institutional partners, including Inserm, and three industrial partners. Together, they bring their expertise in complementary research sectors such as the development and physiology of beta cells, beta cell transplantation, biology of human pluripotent stem cells, polymer chemistry, specialised engineering and epigenetics. The ultimate objective is to develop functional beta cells that produce insulin and respond to glucose, and to enable patients to benefit from these advances in treatment as early as possible.

We hope that the knowledge generated by this project will contribute one day to improved treatment and quality of life for the growing population of people with diabetes,

comments Raphaël Scharfmann, a research director at Inserm Unit 1016 – Institut Cochin, a partner in the HumEn project.

*Stem cells in diabetes treatment

A deficiency of insulin underlies all forms of diabetes, and currently affects 366 million individuals worldwide. In Europe, the number of people with diabetes is estimated at 52.8 million.

Beta cells play a central role in diabetes. They are located in the pancreas and produce insulin, the hormone that controls the transport of energy in the form of glucose to the muscles via the bloodstream. In type 1 diabetes, the immune system destroys the beta cells, whereas in type 2 diabetes, sensitivity to insulin is reduced, causing the body to require increasingly larger quantities of insulin, which the beta cells cannot secrete.

At present, the only solution for replacing destroyed or dysfunctional beta cells is transplantation with a complete pancreas or with islets of functional cells. Only a small number of patients qualify for this treatment, because of the shortage of donors.

The HumEn project is supported through the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement n° HEALTH-F4-2013-602889

Partners in the HumEn project:

DanStem, University of Copenhagen, UCPH, Denmark
Helmholtz Zentrum München, German Research Center for Environmental Health, HMGU, Germany
University of Edinburgh, UEDIN, United Kingdom
Inserm – Institut Cochin, France
Department of Immunology, Genetics and Pathology (IGP), University of Uppsala, UU, Sweden
Developmental Genetics, Max Planck Institute for Heart and Lung Research, MPG, Germany
CYTOO SA, France
MATERIOMICS, The Netherlands

HumEn is becoming part of a vast European consortium working on stem cells
At the same time, the European Commission has just awarded grants to support seven research projects on stem cells. HumEn has already been able to establish collaborations with the PluriMes, Neurostemcellrepair and ThymiStem projects. Together these projects enable Europe to remain at the forefront of stem cell research, in order to create new commercial opportunities and improve the competitiveness of the European biomedical sector. 

Regulatory T cells, ensuring a good immune memory

Regulatory T cells (Treg) are a sub-population of immune cells that prevent each individual from triggering immune reactions against his/her own organs.  In the context of some illnesses, these mechanisms may be defective: in this case, the term “auto-immune reactions” is applied. In this new research, published in the Science review, the team of researchers directed by Sebastian Amigorena (Institut Curie / Inserm U932 Immunity and Cancer unit) demonstrates that the regulatory T cells are also important during immune responses to external antigens, i.e. during infection.

By regulating the interactions between cells with antigens and T cells, Treg prefer engaging “high affinity” cells in terms of antigens, thus boosting the immune response. However, if there are no Treg, this first stage of immune response is defective, leading – in time – to an incorrect memorization process of pathogens and, consequently, to reduced defense mechanisms against infection (for example).

Shedding light on this new property of regulating T cells could prove significant in terms of developing vaccination strategies over time.

crédit photo M Depardieu/Inserm