1] Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, 00100 Rome, Italy [2] Department of Dermatology, University Hospital CHUV, 1011 Lausanne, Switzerland.
Dermatology Unit, NESMOS Department, Sapienza University of Rome, 00100 Rome, Italy.
Nat Commun. 2014 Dec 3;5:5621. doi: 10.1038/ncomms6621.
Psoriasis is a common T-cell-mediated skin disease with 2-3% prevalence worldwide. Psoriasis is considered to be an autoimmune disease, but the precise nature of the autoantigens triggering T-cell activation remains poorly understood. Here we find that two-thirds of patients with moderate-to-severe plaque psoriasis harbour CD4(+) and/or CD8(+) T cells specific for LL37, an antimicrobial peptide (AMP) overexpressed in psoriatic skin and reported to trigger activation of innate immune cells. LL37-specific T cells produce IFN-γ, and CD4(+) T cells also produce Th17 cytokines. LL37-specific T cells can infiltrate lesional skin and may be tracked in patients blood by tetramers staining. Presence of circulating LL37-specific T cells correlates significantly with disease activity, suggesting a contribution to disease pathogenesis. Thus, we uncover a role of LL37 as a T-cell autoantigen in psoriasis and provide evidence for a role of AMPs in both innate and adaptive immune cell activation.
银屑病是一种常见的 T 细胞介导的皮肤疾病，全球患病率为 2-3%。银屑病被认为是一种自身免疫性疾病，但触发 T 细胞激活的确切自身抗原性质仍知之甚少。在这里，我们发现三分之二的中重度斑块状银屑病患者体内存在针对 LL37 的 CD4(+)和/或 CD8(+)T 细胞，LL37 是一种在银屑病皮肤中过度表达的抗菌肽 (AMP)，据报道可引发先天免疫细胞的激活。LL37 特异性 T 细胞产生 IFN-γ，CD4(+)T 细胞也产生 Th17 细胞因子。LL37 特异性 T 细胞可浸润病变皮肤，并可通过四聚体染色在患者血液中追踪。循环中存在 LL37 特异性 T 细胞与疾病活动度显著相关，提示其在疾病发病机制中的作用。因此，我们揭示了 LL37 作为银屑病 T 细胞自身抗原的作用，并为 AMP 在先天和适应性免疫细胞激活中的作用提供了证据。
