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Stepwise induction of CD69 and CD103 marks distinct differentiation stages of mucosal Trms. But the majority of non-mucosal Trm lacks CD103 expression. The expression of CD69 alone cannot faithfully define Trm cells in heavily vascularized non-mucosal tissues, such as the kidney. Here, we found that a subset of kidney Trms downregulated IL-18 receptor during differentiation. Via global transcriptional analysis and parabiosis experiments, we have discovered that the downregulation of interleukin-18 receptor (IL-18R) is associated with the establishment of tissue residency. Together with the expression of CD69, IL-18Rlo exclusively identify tissue-resident cells whereas IL-18Rhi population contains both tissue-resident and migratory ones. Local cytokines including transforming growth factor β (TGF-β) and interferon α (IFN-α)/β as well as TGF-β-dependent suppression of transcription factor Tcf-1 are essential for IL-18R downregulation during kidney Trm differentiation. Together, we identified a convenient surface marker to distinguish bona fide kidney-resident CD8+ T cells as well as underlying molecular mechanisms controlling this differentiation process. © 2020 The Author(s).


Wei Liao, Yong Liu, Chaoyu Ma, Liwen Wang, Guo Li, Shruti Mishra, Saranya Srinivasan, Kenneth Ka-Ho Fan, Haijing Wu, Qianwen Li, Ming Zhao, Xun Liu, Erika L Demel, Xin Zhang, Yuanzheng Qiu, Qianjin Lu, Nu Zhang. The downregulation of IL-18R defines bona fide kidney-resident CD8+ T cells. iScience. 2021 Jan 22;24(1):101975

PMID: 33474536

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