Centre de Référence Maladies Rares


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

FR: Biologie Fondamentale Appliquée à la Médecine

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Dermatology team
Project 2.4

Physiopathology of pigmentation and tissue engineering

keywords: melanocytes, vitiligo, scleroderma, reconstructed epidermis, metabolism


Melanin is the pigment produced by melanocytes that after transfer to surrounding keratinocytes ensures specifically the protection against the harmful effects of ultraviolet and the color of the skin. The skin color and ability to tan conventionally determine six phototypes, going from light to dark. These skin types are not related to a difference in the melanocyte numbers but to their ability to produce pheomelanin (yellow-orange) or eumelanin (brown-black) that is transferred according to its type in pheomelanosomes or eumelanosomes to keratinocytes. The diseases that are associated with local or generalized skin color alteration are generally used as a model for studying the regulation of melanogenesis. To study the physiology of pigmentation, we use reconstructed epidermis, a model that has been qualified based on its capacities to respond to UV and to reproduce the epidermal melanin unit. This model allows us to study the role of epidermal and dermal cells on pigmentation, modeling different pigmentary disorders (using patient cells or genetically modified cells), identifying the key factors (CCN3 in vitiligo), and to evaluate the effect of stimuli supposed to be involved in the etiology of these pathologies. Our main modeled diseases are vitiligo (depigmentation associated with progressive loss of melanocytes), Cole disease (hypo or hyyer pigmentation related to ENNP-1 mutation), scleroderma (fibrosis related to an overproduction of collagen by fibroblasts associated with hypo- and hyper-pigmentation disorders), senile or solar lentigo (hyperpigmentation related to age or sun exposure). We are currently studying the role of oxidative and energy metabolism on physiopathology of these pigmentary disorders and the influence of fibroblasts on pigmentation.

Related publications:

  • A Method for Isolating and Culturing Skin Cells: Application to Endothelial Cells, Fibroblasts, Keratinocytes, and Melanocytes From Punch Biopsies in Systemic Sclerosis Skin. Henrot P, Laurent P, Levionnois E, Leleu D, Pain C, Truchetet ME, Cario M. Front Immunol. () doi: 10.3389/fimmu.2020.566607.
  • Stiffness measurement is a biomarker of skin ageing in vivo. Runel G, Cario M, Lopez-Ramirez N, Malbouyres M, Ruggiero F, Bernard L, Puisieux A, Caramel J, Chlasta J, Masse I. Exp Dermatol. () doi: 10.1111/exd.14195. PMID: 32
  • Dysregulation of CCN3 (NOV) expression in the epidermis of Systemic Sclerosis patients with pigmentary changes Pauline Henrot, Catherine Pain, Alain Taïeb, Marie‐Elise Truchetet, Muriel Cario. Pigment Cell Melanoma Res. () DOI: 10.1111/pcmr.12912
  • Tspan8 Drives Melanoma Dermal Invasion by Promoting ProMMP-9 Activation and Basement Membrane Proteolysis in a Keratinocyte-Dependent Manner. Manale El Kharbili*, Muriel Cario*, Nicolas Béchetoille, Catherine Pain, Claude Boucheix, Françoise Degoul, Ingrid Masse†, Odile Berthier-Vergnes†. * and † contributed equally to this work. Cancers () DOI: 10.3390/cancers12051297
  • Tacrolimus (FK506) ointment combined with Nb-UVB could activate both hair follicle (HF) and dermal melanocyte precursors in vitiligo: the first histopathological and clinical study. Gauthier Y, Almasi-Nasrabadi M, Cario-André M, Pain C, Rakhshan A,Ghalamkarpour F. Arch Dermatol Res. () doi: 10.1007/s00403-020-02068-z
  • Is hyperpigmentation in Systemic Sclerosis a perivascular dermal tattoo? Henrot P, Moisan F, Seneschal J, Taïeb A, Cario M*, Truchetet ME* *contributed equally to this work J Invest Dermatol. () DOI: 10.1016/j.jid.2020.03.937
  • Lentiginosis and cafe-au-lait macules as part of the phenotypic spectrum of PAX3-related disorders. Morice-Picard F, Letertre O, Lasseaux E, Cario-Andre M, Arveiler B, Taieb A. Clin Exp Dermatol. () DOI: 10.1111/ced.14203
  • Decreased CCN3 in Systemic Sclerosis endothelial cells contributes to impaired angiogenesis. Henrot P, Moisan F, Laurent P, Manicki P, Kaulanjan-Checkmodine P, Jolivel V, Rezvani HR, Leroy V, Picard F, Boulon C, Schaeverbeke T, Seneschal J, Lazaro E, Taïeb A, Truchetet ME, Cario M. J Invest Dermatol. () DOI: 10.1016/j.jid.2019.11.0
  • Epidermal keratin 5 expression and distribution is under dermal influence. Cario M, Pain C, Kaulanjan-Checkmodine P, Masia D, Delia G, Casoli V, Costet P, Goussot JF, Guyonnet-Duperat V, Bibeyran A, Ezzedine K, Reymermier C, Andre-Frei V, Taieb A. Pigment Cell Melanoma Res. () doi: 10.1111/pcmr.12844. PMID: 3
  • Oestrogen associated with ultraviolet B irradiation recapitulates the specific melanosome distribution observed in caucasoid melasma. Gauthier Y, Cario M, Pain C, Lepreux S, Benzekri L, Taieb A. Br J Dermatol. () doi: 10.1111/bjd.17453. PubMed P
  • Pigmentation abnormalities in nucleotide excision repair disorders: Evidence and hypotheses. Kasraian Z, Trompezinski S, Cario-André M, Morice-Picard F, Ged C, Jullie ML, Taieb A, Rezvani HR. Pigment Cell Melanoma Res. () DOI: 10.1111/pcmr.12720 PMID: 29
  • Association of skin hyperpigmentation disorders with digital ulcers in systemic sclerosis: analysis of a cohort of 239 patients. Leroy V, Henrot P, Barnetche T, Cario-André M, Darrigade AS, Manicki P, Doutre MS, Lazaro E, Constans J, Barcat D, Vernhes JP, Richez C, Taieb A, Truchetet ME, Seneschal J ; FHU ACRONIM. J Am Acad Dermatol. () PMID: 30092330
  • Epidermal melanocytes in segmental vitiligo show altered expression of E-cadherin, but not P-cadherin. Grill C, Benzekri L, Rubod A, Aktary Z, Ezzedine K, Taïeb A, Gauthier Y, Larue L, Delmas V. Br J Dermatol. () PMID: 29341072
  • Vitiligo-like lesions in patients receiving anti-programmed cell death-1 therapies are distinct from spontaneously occurring active vitiligo. Boniface K, Dutriaux C, Prey S, Taieb A, Seneschal J. J Am Acad Dermatol. () PMID: 29241800
  • Skin equivalents: skin from reconstructions as models to study skin development and diseases. Ali N, Hosseini M, Vainio S, Taïeb A, Cario-André M, Rezvani HR. Br J Dermatol. () 173(2):391-403
  • Altered E-Cadherin Levels and Distribution in Melanocytes Precede Clinical Manifestations of Vitiligo. Wagner RY, Luciani F, Cario-André M, Rubod A, Petit V, Benzekri L, Ezzedine K, Lepreux S, Steingrimsson E, Taieb A, Gauthier Y, Larue L, Delmas V. J Invest Dermatol. () 135(7):1810-9
  • Vitiligo. Picardo M, Dell’Anna M.L, Ezzedine K, Hamzavi I, Harris JE, Parsad D, Taieb A. Nat Rev Dis Primers. () doi:10.1038/nrdp.2015.11
  • Factors secreted by irradiated aged fibroblasts induce solar lentigo in pigmented reconstructed epidermis. Salducci M, André N, Guéré C, Martin M, Fitoussi R, Vié K, Cario-André M. Pigment Cell Melanoma Res. () 27(3):502-4
  • Study of CCN3 (NOV) and DDR1 in normal melanocytes and vitiligo skin. Ricard AS, Pain C, Daubos A, Ezzedine K, Lamrissi-Garcia I, Bibeyran A, Guyonnet-Dupérat V, Taieb A, Cario-André M. Exp Dermatol. () 21(6):411-6

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