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Why do eczema patches caused by skin contact with an allergen reappear in the same areas despite having had time to heal? This is what an International Center for Infectiology Research team with members from Inserm, Université Claude Bernard Lyon 1, Ecole Normale Supérieure de Lyon and CNRS were keen to find out. The researchers discovered that not only do the allergens persist in the skin for several weeks but also that they are not alone in doing so. Indeed, immune cells – known as tissue-resident memory T cells – proliferate at the lesion sites and remain there for long periods, reactivating the onset of eczema patches in the event of re-exposure to the allergen. This research, published in The Journal of Allergy and Clinical Immunology, opens up new perspectives when it comes to understanding the mechanism and treatment of allergic contact dermatitis.

Allergic contact dermatitis (ACD) (a type of eczema) is a skin reaction triggered by exposure to allergens. The resulting inflammation of the upper layers of the skin can last for several days, persists for as long as the area remains in contact with the allergen in question and can even become chronic. It manifests as localized skin rashes (eczema patches) accompanied by itching and burning, and reappears if the healed areas are re-exposed to the allergen.

Tissue-resident memory T (TRM) cells are immune cells that persist in peripheral tissues, such as the skin, over the long term. They contribute to the secondary immune response that – while especially rapid and effective against pathogens encountered previously – can cause the exacerbation of some inflammatory diseases, such as ACD. In the eczema patches caused by ACD, a build-up of TRMs is indeed observed.

A research team at the International Center for Infectiology Research (CIRI), with members from Inserm, Université Claude Bernard Lyon 1, Ecole Normale Supérieure de Lyon and CNRS, studied the contribution of TRMs to the severity and chronicity of ACD in mice. They observed that the TRMs proliferate locally in the areas of the skin in contact with the allergen.

When ACD-induced inflammation resorbs, TRMs gradually accumulate in the epidermis and persist there for several weeks.

The team, in its desire to find out why TRMs persist in the skin, observed that the allergens can remain in the epidermis for much longer than was previously thought (at least one month).

Finally, the researchers observed that the reactivation of the TRMs responsible for the eczema patches was subject to a retro-control enabled by a specific set of inhibitory receptors carried by the TRMs. When re-exposed to a low dose of allergen, these receptors are activated and suppress the activity of the TRMs, thereby preventing an excessive immune reaction.

This research helps to elucidate the role played by the TRMs in the local reappearance of eczema patches. It also shows that the development of therapeutic strategies to prevent the local reactivation of the TRMs through their inhibitory receptors should open up new perspectives in the treatment of ACD.

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Are there ways to improve the efficacy of flu vaccines? Are there markers that could, at the time of vaccination, predict the quality of the immune response several weeks down the line? Thanks to the work of Inserm Research Director Béhazine Combadière’s team at Unit 1135 “Center for Immunology and Infectious Diseases”, the answer to these two major questions is “yes”.

Their findings were published on April 8, 2019 in JCI.

While flu continues to claim lives every year[1], a vaccine exists to protect the populations. And while this vaccine is the best means of preventing the disease and reducing the risk of severe complications and death, it is not 100 % effective. This is due to the fact that its formulation is determined each year by the WHO several months before the epidemic peak and that it is based only on the probability that such and such a flu strain will be in circulation during the coming winter. Flu viruses are highly unpredictable, and the vaccine formulation must change from one year to the next. However, given that 5 to 6 months are needed to develop it, the vaccine does not always target all of the circulating strains.

The team of Béhazine Combadière, Inserm Research Director at Unit 1135 “Center for Immunology and Infectious Diseases”, has been working for years on the impact of vaccine administration routes on the quality of immune responses. The vaccines are usually administered by the muscular route and are effective in inducing humoral responses (production of antibodies), whereas the other immune response component, the cytotoxic response (production of T cells that directly destroy the infected cells) is poorly-induced by this route of administration.

The team studied the utility of administration via the skin – either by intradermal injection or transcutaneous application (via the hair follicles) – in inducing cytotoxic responses during flu vaccination. This involved conducting a phase I/II clinical trial on 60 people between 18 and 45 years of age in collaboration with the Vaccinology CIC led by Dr. Odile Launay. The study, published in JCI, demonstrates that in some subjects the cutaneous routes induce a cytotoxic response following flu vaccination. “This finding argues in favor of considering this vaccine injection route given that it triggers an immune reaction additional to that obtained with a standard vaccination. These cytotoxic responses would be particularly protective in elderly people following flu vaccination. ” explains Combadière.

In addition to these findings, the team brings new elements to the table concerning the specific imprints left by these injection routes in the body. For this, the researchers studied the gene signature of innate immunity, i.e. the expression of the messenger RNA of the genes in the blood the day after vaccination for each administration route. “Since previous findings showed that each administration route had its own innate response, we expected to have three signatures of innate immunity corresponding to the three administration routes, yet our findings only show two. These two signatures are correlated with the immune response of the individual: those that respond to the vaccine by increasing their humoral response and those that respond by inducing a cytotoxic response. “

Among these signatures, a certain number of biomarkers expressed the day after vaccination are thought to be predictive of the quality of immune response three weeks later. “However, these latest findings require other studies to validate the utility of these biomarkers and their future use”, conclude the researchers.

[1] For the winter of 2018-2019, over 2,000 deaths were attributed to the flu according to French Public Health Agency data.