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JAK inhibitors prevent and reverse vitiligo in mice, but do not eliminate established autoreactive T cells in the skin
VN Azzolino, M Grag, L Zapata, J Richmond, R Riding and J Strassner Dermatology, University of Massachusetts Medical School, Worcester, Massachusetts, United States
Vitiligo is an autoimmune disease in which autoreactive, cytotoxic CD8+ T cells destroy the pigment producing melanocytes, resulting in disfiguring, well-defined white patches on the skin.The IFN-gamma-induced chemokines CXCL9 and CXCL10, primarily produced by keratinocytes, are required to recruit autoreactive CD8+ T cells to the skin.Activation of the JAK/STAT pathway is required for efficient production of these chemokines and subsequent T cell recruitment.Targeting this critical pathway has been shown to work effectively for case studies.In this study, we aimed to reduce recruitment of the cytotoxic CD8+ T cells to the skin and prevent subsequent melanocyte death by inhibiting the JAK pathway with the small
molecules inhibitors tofacitinib and ruxolitinib.We tested these JAK inhibitors in our mouse model of vitiligo as both prophylactic and therapeutic treatments.In prophylaxis experiments,these inhibitors lowered the clinical vitiligo scores, chemokine expression of CXCL10 within
the epidermis and dermis, and reduced cytotoxic CD8+ T cell accumulation in skin compartments.In therapeutic treatments, mice with established vitiligo successfully repigmented their lesi**.Surprisingly, repigmentation did not correspond to lower cytotoxic CD8+ T cells
in the epidermal and dermal compartments.This finding echoes the use of secukinumab in psoriasis, where autoimmune signaling is disrupted but the resident memory T cells are not reduced and other recent case studies that also suggest that JAK inhibitors are not durable for vitiligo.These data further support the role of JAK inhibitors as a treatment in both theprogression and maintenance of vitiligo, although they may not be a durable treatment.
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发表于 2019-7-16 00:55:37
发表于 2019-7-16 09:44:57
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