Dynamic trafficking patterns of IL-17-producing γδ T cells are linked to the recurrence of skin inflammation in psoriasis-like dermatitis

作者：Na Liu, Hui Qin, Yihua Cai, Xia Li, Lanqi Wang, Qiannan Xu, Feng Xue, Lihong Chen, Chuanlin Ding, Xiaoling Hu, David Tieri, Eric C. Rouchka, Jun Yan, Jie Zheng · 发表于：EBioMedicine · 年份：2022 · DOI：10.1016/j.ebiom.2022.104136 · 被引用次数：47 · 研究领域：Psoriasis: Treatment and Pathogenesis、Dermatology and Skin Diseases、T-cell and B-cell Immunology

BACKGROUND: Psoriasis recurrence is a clinically challenging issue. However, the underlying mechanisms haven't been fully understood. METHODS: RNAseq analysis from affected skin of psoriatic patients treated with topical glucocorticoid (GC) with different outcomes was performed. In addition, imiquimod (IMQ)-induced mouse psoriasis-like model was used to mimic GC treatment in human psoriasis patients. Skin tissues and draining and distant lymph nodes (LNs) were harvested for flow cytometry and histology analyses. FINDINGS: RNAseq analysis revealed that chemokine and chemokine receptor gene expression was decreased in post-treated skin compared to pre-treated samples but was subsequently increased in the recurred skin. In IMQ-induced mouse psoriasis-like model, we found that γδT17 cells were decreased in the skin upon topical GC treatment but surprisingly increased in the draining and distant LNs. This redistribution pattern lasted even two weeks post GC withdrawal. Upon IMQ re-challenge on the same site, mice previously treated with GC developed more severe skin inflammation. There were γδT17 cells migrated from LNs to the skin. This dynamic trafficking was dependent on CCR6 as this phenomenon was completely abrogated in CCR6-deficient mice. In addition, inhibition of lymphocyte egress prevented this heightened skin inflammation induced by IMQ rechallenge. INTERPRETATION: Redistribution of pathogenic γδT17 cells may be vital to prevent disease recurrence and this model of psor...