Centre de Référence Maladies Rares

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Biotherapy of genetic diseases, inflammatory disorders and cancers (BMGIC)

FR: Biologie Fondamentale Appliquée à la Médecine

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ATIP-AVENIR team (Immuno-dermatology)
Project 3.1

Vitiligo physiopathology

keywords: Vitiligo physiopathology

Description:

overview of vitiligo pathogenesis
The main goal of the ATIP-Avenir project is to develop basic research program on inflammatory dermatoses, in particular vitiligo, and to consolidate the collaboration with the department of dermatology 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. In accordance, 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 oxidative stress and metabolic responses in melanocytes will be assessed in close collaboration with the expertise of the dermatology team. Moreover, the interaction between the immune response and melanocytes will be better studied using epidermal reconstruction with melanocytes, which has allowed the modelization of the melanocytorrhagy hypothesis formulated by our group in 2003.
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 will investigate 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 will be given to the phenotype and function of these cells. Ultimately, our goal is to define a specific target that will eventually lead to novel therapeutic interventions to improve vitiligo management.
Watch the Prof Julien Seneschal’ talk at the last European for Dermatological Research meeting in 2017
Prof Julien Seneschal’s talk at the ESDR meeting 2017

Related publications:

  • Cell delivery using microneedle devices: a new approach to treat depigmenting disorders. Boniface K, Taieb A, Seneschal J. Br J Dermatol. (2018-03) PMID: 29595229
  • Vitiligo: Focus on Clinical Aspects, Immunopathogenesis, and Therapy. Boniface K, Seneschal J, Picardo M, Taïeb A Clin Rev Allergy Immunol. (2018-02) DOI: 10.1007/s12016-017-8622
  • Vitiligo Skin Is Imprinted with Resident Memory CD8 T Cells Expressing CXCR3. Boniface K, Jacquemin C, Darrigade AS, Dessarthe B, Martins C, Boukhedouni N, Vernisse C, Grasseau A, Thiolat D, Rambert J, Lucchese F, Bertolotti A, Ezzedine K, Taieb A, Seneschal J. J Invest Dermatol (2018-02) PMID: 28927891
  • Toxicity profiles of immunotherapy. Cousin S, Seneschal J, Italiano A. Pharmacol Ther. (2018-01) PMID: 28716652
  • HSP70 potentiates interferon-alpha production by plasamcytoid dendritic cells : relevance for cutaneous lupus and vitiligo pathogenesis. C. Jacquemin, J. Rambert, S. Guillet, D. Thiolat, N Boukhedouni, MS Doutre, AS Darrigade, K Ezzedine, P. Blanco, A. Taieb, K. Boniface, J Seneschal. Brit J Dermatol (2017-11)
  • Vitiligo-like lesions occurring in patients receiving anti-PD-1 therapies are clinically and biologically distinct from vitiligo M. Larsabal*, A. Marti1* , C. Jacquemin, J. Rambert, D. Thiolat, L. Dousset, A. Taieb, C. Dutriaux, S. Prey, K. Boniface*, J. Seneschal. *equally contribution J Am Acad Dermatol (2017-05) DOI: 10.1016/j.jaad.2016.10.
  • OX40 Ligand Contributes to the Pathogenesis of Autoiimunity by Promoting T follicular Helper Response. * equally contribution C. Jacquemin*, N. Schmitt*, C. Contin-Bordes*, Y. Liu, P. Narayanan, J. Seneschal, T. Maurouard, D. Dougall, E. Spence Davizon, H. Dumortier, I. Douchet, L. Raffray, C. Richez, E. Lazaro, P. Duffau, M.E. Truchetet, L. Khoryati, P. Mercié, L. Couzi, P. Merville, T. Schaeverbeke, J.F. Viallard, J.L. Pellegrin, J.F. Moreau, S. Muller, R.L. Coffman, V. Pascual, H. Ueno* and P. Blanco*. *equally contribution Immunity (2014) 42;1159-70
  • Type I Interferon signature in the initiation of the immune response in vitiligo. A. Bertolotti, K. Boniface, B. Vergier, MD. Mossalayi, A. Taieb, K. Ezzedine, J. Seneschal. Pigment Cell Melanom Res. (2014) 27:398-407
  • Human Epidermal Langerhans Cells Maintain Immune Homeostasis in Skin by Activating Skin Resident Regulatory T Cells. J. Seneschal, R.A.Clark, A. Gehad, Clare M. Baecher-Allan, T.S. Kupper. Immunity. (2012) 873-8
  • Prostaglandin E2 regulates Th17 cell differentiation and function through cyclic-AMP and EP2/EP4 receptor signaling Boniface K, Bak-Jensen KS, Li Y, Blumenschein WM, McGeachy MJ, McClanahan TK, McKenzie BS, Kastelein RA, Cua DJ, de Waal Malefyt R. J. Exp. Med. (2009) 206(3):535-548.

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