Crosstalk between immune and epidermal cells

The immuno-dermatology group is focused on the immune mechanisms involved in skin inflammatory diseases, in particular vitiligo, the most common skin depigmenting disorder.

TBased on a strong clinical research program dedicated to this disease in the department of Dermatology and the support of international groups (such as Vitiligo European Task Force), we have developed basic and translational research studies exploring both the innate and the adaptive immune responses in vitiligo, leading to the discovery of the role of the Type I Interferon signature in the initiation of the disease together with the involvement of resident memory T cells expressing CXCR3. We now explore the role of these cells and inflammatory cytokines produced on the function, survival and adhesion of melanocytes, the cells responsible for pigmentation. Our work aims to better understand the link between immunity and melanocyte loss in vitiligo. Patents have been submitted for the development of targeted therapies in Vitiligo and close collaborations have been developed with national and international academic teams and industrial partners. Moreover, our research could be generalized to pigmentation disorders affecting inflammatory skin diseases, such as psoriasis, atopic dermatitis, or scleroderma.

Our team is part of the Fédération Hospitalo-Universitaire ACRONIM, University of Bordeaux and is linked to the Department of Dermatology, National reference for Rare Skin Diseases and the Auto-immune and Inflammatory skin diseases Unit of the University Hospital of Bordeaux.

Our research projects:

1 · Vitiligo and pigmentary disorders associated with inflammation.

The main goal of the immuno-dermatology project is to develop basic and translational research programs on vitiligo and pigmentary changes associated with skin inflammation, and to consolidate the collaboration with the department of dermatology (National Reference Center for Skin Diseases) and the clinical research program already internationally well recognized in the field.

Vitiligo remains to date the major depigmenting disorder with a real social impact and without effective treatment. The classical hallmark of vitiligo is the disappearance of melanocytes. While several theories have been proposed to explain the pathomechanism of the disease, intrinsic defects of melanocytes with local increased production of ROS, associated with an exaggerated immune response, appear
important. The impact of the immune response in vitiligo will be based on the new concepts of skin immune surveillance. Several immune cell types populate human healthy skin, including dendritic cells, which have a crucial role at the interface between the environment, the epithelium, and adaptive immune cells. In addition, recent progresses have been made in the description and function of skin immune T cells and the newly described skin resident effector memory T cells (TRM). Skin TRM are characterized by the expression of CD69 and CD103 and have the capacity to locally proliferate in skin, and produce large amount of multiple cytokines under local stimulation. Precisely, our project investigates the role of T, especially TRM cell subsets and the soluble factors produced in the process leading to melanocyte loss in vitiligo through both clinical and fundamental research studies. A particular attention is given to the phenotype and function of these cells. Ultimately, our goal, based on our ongoing research, is to define a specific target that will eventually lead to novel therapeutic interventions to improve vitiligo management.
Additionally, we aim to decipher the role of the immune response leading to melanocyte loss, particularly on the function, survival, and adhesion of melanocytes. Understanding the interplay between the immune response and the deregulation of the function and phenotype of melanocytes remain important. This interaction between the immune response and melanocytes is better studied using epidermal reconstruction with melanocytes and in-vivo models, which has allowed the modelization of the melanocytorrhagy hypothesis formulated by our group in 2003. Our recently published research identifies new mechanisms for the understanding of the mechanism leading to the loss of melanocytes in vitiligo (patents: WO2018109222A1 and EP 3336175 A1, JCI insight 2020). We showed that the combined activity of two pro-inflammatory cytokines interferon (IFN)-g and tumor necrosis factor (TNF)-a induces melanocyte detachment rather than death in vitro and in vivo and this phenomenon is dependent of the increased expression of activated matrix metalloproteinase 9 (MMP9), leading to the cleavage of E-cadherin, important for the stability of melanocytes.
Moreover, we are developing models useful for the understanding of pigmentary disorders associated with inflammation that could be seen during the course of chronic inflammatory diseases such as psoriasis, atopic dermatitis or scleroderma.

Further information: https://vitiligo-bordeaux.org

2 · Inflammatory Skin Diseases: psoriasis, atopic dermatitis, alopecia areata.

In collaboration with Dr Mei Li, (IGBMC: Institut de Génétique et Biologie Moléculaire et Cellulaire, Strasbourg, France), we have recently demonstrated a new mechanism of a molecule classically used for the treatment of psoriasis (a frequent and chronic skin inflammatory associated with erythematous plaques with flakes): calcipotriol (Vitamin D analogue). Calcipotriol used alone or in combination with
corticosteroid efficiently disrupts the IL-36 and IL-23/IL-17 positive feedback loop, thus revealing a mechanism underlying the superior efficacy of calcipotriol and corticosteroid combination therapy for psoriasis.
Regarding Atopic Dermatitis: a skin chronic disorders responsible for major pruritus affecting the quality of life of patients; a collaborative project is currently conducted with Dr Charles Bodet (LITEC: Laboratoire Inflammation, Tissus épithéliaux et Cytokines, Université de Poitiers, France). This project received the support of “Région Nouvelle-Aquitaine” and will better decipher the complex interaction
between the immune response, the skin barrier and the microbiota. Moreover another collaborative project is also conducted with Dr Mei Li (IGBMC) on the role of a small population of immune cells called “Basophils”.

Collaborations

Prof Franc MOREL: LITEC EA 4331, Poitiers
Dr Lionel LARUE Institut Curie, INSERM U1021, Orsay

Dr Mei Li IGBMC, Strasbourg

People Involved

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