Dehner Carina A, Ruff William E, Greiling Teri, Pereira Márcia S, Redanz Sylvio, McNiff Jennifer, Girardi Michael, Kriegel Martin A
Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.
Department of Pathology & Immunology, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA.
JID Innov. 2021 Dec 16;2(2):100084. doi: 10.1016/j.xjidi.2021.100084. eCollection 2022 Mar.
Cutaneous T-cell lymphoma (CTCL) is a life-debilitating malignancy of lymphocytes homing to the skin. Although CTCL is thought to arise from a combination of genetic, epigenetic, and environmental factors, specific triggers are unclear. The skin is colonized by a unique microbiota and is heavily influenced by its interactions. We hypothesized that adaptive immune responses to skin commensals lead to clonal T-cell proliferation and transformation in the appropriate genetic background. We therefore collected lesional and nonlesional skin microbiota from patients with CTCL to study T cell interactions using skin T cell explants and peripheral, skin-homing CD4 T cells. By various methods, we identified in CTCL lesions, a rare human commensal in healthy skin, and showed that it can induce malignant T cell activation and cytokine secretion. Taken together, our data suggest microbial triggers in the skin microbiota of patients with CTCL as potential instigators of tumorigenesis.
皮肤T细胞淋巴瘤（CTCL）是一种使身体衰弱的淋巴细胞归巢至皮肤的恶性肿瘤。尽管CTCL被认为是由遗传、表观遗传和环境因素共同作用引起的，但具体触发因素尚不清楚。皮肤定植有独特的微生物群，并受其相互作用的严重影响。我们推测，在适当的遗传背景下，对皮肤共生菌的适应性免疫反应会导致克隆性T细胞增殖和转化。因此，我们收集了CTCL患者的皮损和非皮损皮肤微生物群，以利用皮肤T细胞外植体和外周归巢至皮肤的CD4 T细胞研究T细胞相互作用。通过各种方法，我们在CTCL皮损中鉴定出一种在健康皮肤中罕见的人体共生菌，并表明它可诱导恶性T细胞活化和细胞因子分泌。综上所述，我们的数据表明，CTCL患者皮肤微生物群中的微生物触发因素可能是肿瘤发生的潜在诱因。
