免疫学
免疫系统
特应性皮炎
树突状细胞
细胞毒性T细胞
胸腺基质淋巴细胞生成素
疾病
T细胞
FOXP3型
生物
医学
病理
生物化学
体外
作者
Christine Bangert,Katharina Rindler,Thomas Krausgruber,Natalia Alkon,Felix M. Thaler,Harald Kurz,Tanya Ayub,Denis Demirtas,Nikolaus Fortelny,Vera Vorstandlechner,Wolfgang Bauer,Tamara Quint,Michael Mildner,Constanze Jonak,Adelheid Elbe‐Bürger,Johannes Griss,Christoph Bock,Patrick M. Brunner
出处
期刊:Science immunology
[American Association for the Advancement of Science (AAAS)]
日期:2021-01-08
卷期号:6 (55)
被引量:66
标识
DOI:10.1126/sciimmunol.abe2749
摘要
Therapeutic options for autoimmune diseases typically consist of broad and targeted immunosuppressive agents. However, sustained clinical benefit is rarely achieved, as the disease phenotype usually returns after cessation of treatment. To better understand tissue-resident immune memory in human disease, we investigated patients with atopic dermatitis (AD) who underwent short-term or long-term treatment with the IL-4Rα blocker dupilumab. Using multi-omics profiling with single-cell RNA sequencing and multiplex proteomics, we found significant decreases in overall skin immune cell counts and normalization of transcriptomic dysregulation in keratinocytes consistent with clearance of disease. However, we identified specific immune cell populations that persisted for up to a year after clinical remission while being absent from healthy controls. These populations included LAMP3+CCL22+ mature dendritic cells, CRTH2+CD161+ T helper ("TH2A") cells, and CRTAM+ cytotoxic T cells, which expressed high levels of CCL17 (dendritic cells) and IL13 (T cells). TH2A cells showed a characteristic cytokine receptor constellation with IL17RB, IL1RL1 (ST2), and CRLF2 expression, suggesting that these cells are key responders to the AD-typical epidermal alarmins IL-25, IL-33, and TSLP, respectively. We thus identified disease-linked immune cell populations in resolved AD indicative of a persisting disease memory, facilitating a rapid response system of epidermal-dermal cross-talk between keratinocytes, dendritic cells, and T cells. This observation may help to explain the disease recurrence upon termination of immunosuppressive treatments in AD, and it identifies potential disease memory-linked cell types that may be targeted to achieve a more sustained therapeutic response.
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