免疫学
生物
银屑病
CD8型
抗原
细胞毒性T细胞
T细胞
炎症
化脓性链球菌
T淋巴细胞
免疫系统
体外
金黄色葡萄球菌
遗传学
生物化学
细菌
作者
Yi‐Ling Chen,Jessica Soo Weei Ng,Rosana Ottakandathil Babu,Jeongmin Woo,Janina Nahler,Clare S. Hardman,Prathiba Kurupati,Lea Nußbaum,Fei Gao,Tao Dong,Kristin Ladell,David A. Price,David A. Duncan,David W. Johnson,Uzi Gileadi,Hashem Koohy,Graham S. Ogg
出处
期刊:Science immunology
[American Association for the Advancement of Science (AAAS)]
日期:2023-06-08
卷期号:8 (84)
被引量:3
标识
DOI:10.1126/sciimmunol.add9232
摘要
Group A Streptococcus (GAS) infection is associated with multiple clinical sequelae, including different subtypes of psoriasis. Such post-streptococcal disorders have been long known but are largely unexplained. CD1a is expressed at constitutively high levels by Langerhans cells and presents lipid antigens to T cells, but the potential relevance to GAS infection has not been studied. Here, we investigated whether GAS-responsive CD1a-restricted T cells contribute to the pathogenesis of psoriasis. Healthy individuals had high frequencies of circulating and cutaneous GAS-responsive CD4+ and CD8+ T cells with rapid effector functions, including the production of interleukin-22 (IL-22). Human skin and blood single-cell CITE-seq analyses of IL-22-producing T cells showed a type 17 signature with proliferative potential, whereas IFN-γ-producing T cells displayed cytotoxic T lymphocyte characteristics. Furthermore, individuals with psoriasis had significantly higher frequencies of circulating GAS-reactive T cells, enriched for markers of activation, cytolytic potential, and tissue association. In addition to responding to GAS, subsets of expanded GAS-reactive T cell clones/lines were found to be autoreactive, which included the recognition of the self-lipid antigen lysophosphatidylcholine. CD8+ T cell clones/lines produced cytolytic mediators and lysed infected CD1a-expressing cells. Furthermore, we established cutaneous models of GAS infection in a humanized CD1a transgenic mouse model and identified enhanced and prolonged local and systemic inflammation, with resolution through a psoriasis-like phenotype. Together, these findings link GAS infection to the CD1a pathway and show that GAS infection promotes the proliferation and activation of CD1a-autoreactive T cells, with relevance to post-streptococcal disease, including the pathogenesis and treatment of psoriasis.
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