Department of Dermatology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Department of Dermatology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
J Invest Dermatol. 2019 Apr;139(4):769-778. doi: 10.1016/j.jid.2018.10.032. Epub 2018 Nov 10.
Tissue resident memory T cells (Trm) form in the skin in vitiligo and persist to maintain disease, as white spots often recur rapidly after discontinuing therapy. We and others have recently described melanocyte-specific autoreactive Trm in vitiligo lesions. Here, we characterize the functional relationship between Trm and recirculating memory T cells (Tcm) in our vitiligo mouse model. We found that both Trm and Tcm sensed autoantigen in the skin long after stabilization of disease, producing IFN-γ, CXCL9, and CXCL10. Blockade of Tcm recruitment to the skin with FTY720 or depletion of Tcm with low-dose Thy1.1 antibody reversed disease, indicating that Trm cooperate with Tcm to maintain disease. Taken together, our data provide characterization of skin memory T cells in vitiligo, demonstrate that Trm and Tcm work together during disease, and indicate that targeting their survival or function may provide novel, durable treatment options for patients.
组织驻留记忆 T 细胞（Trm）在白癜风的皮肤中形成，并持续存在以维持疾病，因为在停止治疗后，白斑往往会迅速复发。我们和其他人最近在白癜风病变中描述了黑素细胞特异性自身反应性 Trm。在这里，我们在我们的白癜风小鼠模型中描述了 Trm 和循环记忆 T 细胞（Tcm）之间的功能关系。我们发现，在疾病稳定后很久，Trm 和 Tcm 都在皮肤中感知自身抗原，产生 IFN-γ、CXCL9 和 CXCL10。用 FTY720 阻断 Tcm 向皮肤的募集或用低剂量 Thy1.1 抗体耗尽 Tcm 可逆转疾病，表明 Trm 与 Tcm 合作维持疾病。总之，我们的数据提供了白癜风皮肤记忆 T 细胞的特征描述，证明了 Trm 和 Tcm 在疾病过程中协同作用，并表明靶向它们的存活或功能可能为患者提供新的、持久的治疗选择。
