西湖大学董晨小组近日取得一项新成果。经过不懈努力，他们的最新研究探明了干细胞样上皮内γδ T细胞的效应分化是宿主防御感染所必需的。这一研究成果发表在2026年2月25日出版的国际学术期刊《免疫学》上。

课题组研究人员发现了两个不同的γδIEL亚群：CD160⁺TCF1⁺BCL6⁺干细胞样细胞和颗粒酶B⁺BLIMP1⁺效应样细胞，后者表现出细胞毒性活性。干细胞样γδIELs在微生物群和病原体感染下分化为效应样细胞。白细胞介素12（IL-12）与IL-15和T细胞受体（TCR）信号共同激活STAT4-BLIMP1通路，诱导效应物分化，而IL-12信号通路是其细胞毒性功能所必需的。TCF1转录因子缺失减少了干细胞样γδIELs，而BCL6缺失选择性地增加了效应样γδIELs。

相比之下，转录因子BLIMP1的缺失不仅阻止了效应物样γδIELs的发展，而且还损害了肠源性病原体的清除。综上所述，这些发现定义了两个功能不同的γδIEL亚群，它们具有将肠道中微生物和细胞因子信号与细胞毒性γδT细胞功能联系起来的分层调节程序。

研究人员表示，TCRγδ⁺上皮内淋巴细胞（γδ iel）对维持肠道内稳态至关重要，但其功能调控尚不完全清楚。

附：英文原文

Title: Effector differentiation by stem-like intraepithelial γδ T cells is required for host defense against infection

Author: Shiyuan Xie, Qi Xing, Qian Zhang, Hao Zhang, Qinli Sun, Qiuyan Lan, Zhiyu Gu, Birui Pan, Peng Wei, Yujie Fu, Xiaohu Wang, Chen Dong

Issue&Volume: 2026-02-25

Abstract: TCRγδ+ intraepithelial lymphocytes (γδIELs) are crucial for maintaining intestinal homeostasis, yet their functional regulation remains incompletely understood. Here, we demonstrated two distinct γδIEL subsets: CD160+TCF1+BCL6+ stem-like and granzymeB+BLIMP1+ effector-like cells, with the latter exhibiting cytotoxic activity. Stem-like γδIELs differentiated into effector-like cells in response to microbiota and pathogen infection. Interleukin 12 (IL-12), in cooperation with IL-15 and T cell receptor (TCR) signaling, activated a STAT4-BLIMP1 pathway to induce effector differentiation, while IL-12 signaling was required for their cytotoxic function. TCF1 transcription factor deletion reduced stem-like but not effector-like γδIELs, while BCL6 deficiency increased effector-like γδIELs selectively. By contrast, the absence of the transcription factor BLIMP1 not only abolished the development of effector-like γδIELs but also impaired the clearance of enterogenous pathogens. Taken together, these findings define two functionally distinct γδIEL subsets with a hierarchical regulatory program linking microbial and cytokine signals to cytotoxic γδT cell function in the gut.

DOI: 10.1016/j.immuni.2026.01.006

Source: https://www.cell.com/immunity/abstract/S1074-7613(26)00027-0