2026
CXCR6 defines a distinct resident state in γδ T cells for protecting from liver cirrhosis
Publication Information
Title:CXCR6 defines a distinct resident state in γδ T cells for protecting from liver cirrhosis
Author(s): Jiahao Ji, Zhitao Chen, Wenjing He, Yanxu Chen, Dongmei Ye, Yingqian Zhong, Xiaomin Shi, Xiaojun Ouyang, Zhimin Zeng, Qianyu Ye, Xiaoshun He, Zhinan Yin, Jianlei Hao, Yifang Gao
Journal Name, Year, Volume(Issue): Page range:
Hepatology, 2026 (In Press)
DOI:10.1097/HEP.0000000000001643
Abstract:
Background and aims: Liver cirrhosis, a leading global cause of mortality, is marked by progressive fibrosis and immune dysregulation. Tissue-resident memory T (TRM) cells, particularly γδ T cells, are emerging as critical regulators of hepatic immunity; however, their role in fibrogenesis remains poorly understood.
Approach and results: Through single-cell RNA sequencing and flow cytometry, we show that CD69 + CXCR6 + γδ T cells are enriched in healthy livers and produce IFN-γ and IL-2 but are significantly depleted in cirrhotic tissue, correlating with disease severity. In a murine fibrosis model, CXCR6 + γδ T cells limited fibrosis progression by inducing hepatic stellate cell apoptosis via FasL-Fas signaling. Adoptive transfer of CXCR6+ γδ T cells significantly mitigated fibrosis, whereas CXCR6- γδ T cells showed no such effect.
Conclusions: Liver-resident CD69+ CXCR6+ γδ T cells constitute a protective immune subset that limits fibrosis development and progression. Enhancing the function or abundance of this population may offer a promising immunotherapeutic strategy for liver cirrhosis.
