The antimicrobial peptide LL37 is a T-cell autoantigen in psoriasis
The antimicrobial peptide LL37 is a T-cell autoantigen in psoriasis
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DOI：
10.1038/ncomms6621
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发表时间：
2014-12-01
影响因子：
16.6
通讯作者：
Frasca, Loredana
中科院分区：
文献类型：
--
作者：
Lande, Roberto;Botti, Elisabetta;Frasca, Loredana
牛皮癣是一种常见的 T 细胞介导的皮肤病，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 细胞激活的自身抗原的确切性质仍然知之甚少。在这里，我们发现三分之二的中重度斑块型银屑病患者体内含有 LL37 特异性的 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)，据报道可触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 细胞可以浸润病变皮肤，并且可以通过四聚体染色在患者血液中进行追踪。循环中 LL37 特异性 T 细胞的存在与疾病活动显着相关，表明其对疾病发病机制有贡献。因此，我们揭示了 LL37 作为 T 细胞自身抗原在银屑病中的作用，并为 AMP 在先天性和适应性免疫细胞激活中的作用提供了证据。
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-gamma, and CD4(+) Tcells also produce Th17 cytokines. LL37-specific Tcells 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.