Immunology of skin allergy and vaccination

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Research themes

Our research field targets the pathophysiology of inflammatory skin diseases, especially eczema (contact dermatitis and atopic eczema) and drug allergy. These diseases are the consequence of the failure of immune tolerance to allergens present in our daily environment.

Eczemas (contact eczema / atopic eczema)
Contact eczema is induced by chemicals called haptens, endowed with reactive functions to self-proteins. Atopic eczema is induced by contact with proteins of the environment (dust mites, flour, pollen, cat hair …). Both diseases are very common inflammatory dermatoses in industrialized countries (Figure 1). They are defined as delayed hypersensitivity reactions. Indeed, while the vast majority of individuals do not develop adaptive immunity and T lymphocytes (TL) following repeated contacts with specific allergens (tolerance), these inflammatory dermatoses are induced in sensitised patients after recruitment and activation in the skin of cytotoxic LT (CTLs) that can induce apoptosis of keratinocytes with the allergen (immunohistological major characteristic of eczema).

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Drug allergy
There are many forms of drug allergy. We are particularly interested in maculopapular exanthema (MPE), frequent and benign drug eruptions, and DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) or toxic epidermal necrolysis (TEN), rare but severe and engaging the prognosis in 30% of cases (Figure 2). The pathophysiological mechanisms that lead to the occurrence of these diseases after oral or parenteral administration of drugs remain few known, partly because of the lack of appropriate experimental models. The current paradigm posits that symptoms would develop according similar mechanisms to those described in eczema, with a central role of T cells specific to drugs in the development of skin lesions.

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Goals and applications of our work:
Our team seeks to decipher the mechanisms by which haptens, drugs or other protein allergens promote or circumvent immune tolerance and induce allergic response, using both mouse models and patient samples.
Our work has applications for the development of immunological tests (in vitro / in vivo) for the diagnosis of drug allergy, especially beta-lactams, and for predicting sensitizing properties of chemicals in general. Our ultimate goal is to develop new strategies to restore the skin tolerance to allergens.
Finally, our expertise in skin immunity led us to participate in R & D projects with Lyonbiopôle to develop new approaches to vaccination and diagnosis using the intradermal route.

The methods we use are:
i-animal testing: our lab has a long expertise in the use and development of mouse models of allergic skin diseases.
ii-translational medicine: patient samples (blood, skin biopsies, blister liquid) are treated daily. To this end, we work closely with four clinical teams at the South Lyon Hospital: a) the Department of Allergy and Clinical Immunology, b) the Clinical Research Unit URCI, c) Allergobiotec and d) Regional Competence Centre for Drug Allergy.
iii-cell immunology / Flow Cytometry / qPCR-chips to DNA / Immunohistology / Immunohistochemistry: We used standard and new technologies to characterize skin and cell samples.

 

Main achievements

Our work led to better knowledge of the pathophysiology of allergic skin diseases (Figure 3). In particular, we showed that:

  • The CD8 + cytotoxic T lymphocytes (CTLs) are required for the initiation of allergic contact dermatitis, atopic eczema and skin lesions of drug allergy.
  • A subset of T regulators lymphocytes (CD4 + FoxP3 + ICOS +) discrete and highly suppressive actively controls the expansion and activation of effector CTLs in these allergic diseases.

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Sponsors

Inserm, Université, ANR, FUI, HCL, SRD, SFA, SFI, partenaires industriels

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