Epidermal Th22 and Tc17 Cells Form a Localized Disease Memory in Clinically Healed Psoriasis
Epidermal Th22 and Tc17 Cells Form a Localized Disease Memory in Clinically Healed Psoriasis
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DOI：
10.4049/jimmunol.1302313
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发表时间：
2014-04-01
影响因子：
4.4
通讯作者：
Eidsmo, Liv
中科院分区：
文献类型：
--
作者：
Cheuk, Stanley;Wiken, Maria;Eidsmo, Liv
银屑病是一种常见的慢性炎症性皮肤病，其中T细胞起着关键作用。有效的治疗可以愈合皮肤而不留下疤痕，但通常牛皮癣会在以前受影响的区域复发。已经提出了皮肤内的致病性记忆，但这种部位特异性疾病记忆的性质尚不清楚。组织常驻记忆T （T- rm）细胞被认为在解决病毒性皮肤感染后的免疫中起作用。由于T-RM定位于皮肤的表皮腔室，可能导致银屑病的组织病理。在这项研究中，我们调查了消退的牛皮癣病变是否含有T-RM细胞，这些细胞具有维持和潜在驱动复发性疾病的能力。研究了三种常见有效的治疗方法，窄带uvb治疗和长期全身抑制tnf - α或IL-12/23信号的生物治疗。表皮T细胞在银屑病中高度活化，CD8 T细胞表达T- rm标记物的比例很高。在解决牛皮癣中，皮肤淋巴细胞相关的Ag、CCR6、CD103和IL-23R表达表皮CD8 T细胞群高度富集。表达T- rm标记物CD103的表皮CD8 T细胞对IL-17A的体外刺激产生应答，而在tnf - α抑制长达6年后，表皮CD4 T细胞对IL-22的产生产生应答。我们的数据表明，表皮T-RM细胞保留在消退的银屑病中，这些细胞能够产生在银屑病发病中起关键作用的细胞因子。我们提供了银屑病部位特异性T细胞驱动的疾病记忆的潜在机制。
Psoriasis is a common and chronic inflammatory skin disease in which T cells play a key role. Effective treatment heals the skin without scarring, but typically psoriasis recurs in previously affected areas. A pathogenic memory within the skin has been proposed, but the nature of such site-specific disease memory is unknown. Tissue-resident memory T (T-RM) cells have been ascribed a role in immunity after resolved viral skin infections. Because of their localization in the epidermal compartment of the skin, T-RM may contribute to tissue pathology during psoriasis. In this study, we investigated whether resolved psoriasis lesions contain T-RM cells with the ability to maintain and potentially drive recurrent disease. Three common and effective therapies, narrowband-UVB treatment and long-term biologic treatment systemically inhibiting TNF-alpha or IL-12/23 signaling were studied. Epidermal T cells were highly activated in psoriasis and a high proportion of CD8 T cells expressed T-RM markers. In resolved psoriasis, a population of cutaneous lymphocyte-associated Ag, CCR6, CD103, and IL-23R expressing epidermal CD8 T cells was highly enriched. Epidermal CD8 T cells expressing the T-RM marker CD103 responded to ex vivo stimulation with IL-17A production and epidermal CD4 T cells responded with IL-22 production after as long as 6 y of TNF-alpha inhibition. Our data suggest that epidermal T-RM cells are retained in resolved psoriasis and that these cells are capable of producing cytokines with a critical role in psoriasis pathogenesis. We provide a potential mechanism for a site-specific T cell-driven disease memory in psoriasis.