Oka Tomonori, Hasegawa Tatsuya, Lee Truelian, Oliver-Garcia Valeria S, Mortaja Mahsa, Azin Marjan, Horiba Satoshi, Smith Sabrina S, Khattab Sara, Trerice Kathryn E, Chen Steven T, Semenov Yevgeniy R, Demehri Shadmehr
Center for Cancer Immunology is a part of Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
JID Innov. 2024 Nov 7;5(1):100324. doi: 10.1016/j.xjidi.2024.100324. eCollection 2025 Jan.
Adult human skin contains nearly twice as many T cells as the peripheral blood, which include tissue-resident memory T cells. However, the precise mechanisms maintaining tissue-resident memory T cells in the healthy skin remain unclear. Using normal human skin samples, we find that Langerhans cells (LCs) contact T cells in the epidermis of the elderly. LCs with high HLA-II, CD86, and PD-L2 expression directly contacted PD-1 tissue-resident memory T cells and CTLA-4 regulatory T cells in the epidermis, indicating an axis of peripheral tolerance in a steady state. Environmental insults, UVB radiation, and hapten downregulated HLA-II and CD86 on LCs in the epidermis, suggesting that disruption of LC-T cell tolerogenic axis contributes to skin inflammation. Interestingly, immune checkpoint blockade therapy was associated with decreased epidermal LC-T cell contact in the normal skin of patients with cancer affected by cutaneous immune-related adverse events. Collectively, our findings indicate that LCs may contribute to T cell tolerance in the epidermis.
成年人类皮肤中的T细胞数量几乎是外周血的两倍，其中包括组织驻留记忆T细胞。然而，在健康皮肤中维持组织驻留记忆T细胞的确切机制仍不清楚。使用正常人类皮肤样本，我们发现朗格汉斯细胞（LCs）在老年人的表皮中与T细胞接触。高表达HLA-II、CD86和PD-L2的LCs直接与表皮中的PD-1组织驻留记忆T细胞和CTLA-4调节性T细胞接触，表明在稳态下存在外周耐受轴。环境损伤、紫外线B辐射和半抗原会下调表皮中LCs上的HLA-II和CD86，这表明LC-T细胞耐受轴的破坏会导致皮肤炎症。有趣的是，免疫检查点阻断疗法与患有皮肤免疫相关不良事件的癌症患者正常皮肤中表皮LC-T细胞接触的减少有关。总的来说，我们的研究结果表明LCs可能有助于表皮中的T细胞耐受。
