Volume 31, No 12, Dec 2021

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 31 Issue 12, December 2021: 1291-1307

ORIGINAL ARTICLES

Integrin αEβ7+ T cells direct intestinal stem cell fate decisions via adhesion signaling

Shiyang Chen^1,2,† , Yajuan Zheng^2,† , Xiaojuan Ran^2,† , Hui Du² , Hua Feng³ , Lei Yang² , Yating Wen² , Changdong Lin² , Shihui Wang² , Mengwen Huang² , Zhanjun Yan⁴ , Dianqing Wu⁵ , Hongyan Wang^1,2 , Gaoxiang Ge^1,2 , An Zeng^2,* , Yi Arial Zeng^1,2,* , Jianfeng Chen^1,2,*

¹School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, Zhejiang, China
²State Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China
³Omics Core, Bio-Med Big Data Center, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China
⁴Department of Orthopedics, Suzhou Ninth People’s Hospital, Soochow University, Suzhou, Jiangsu, China
⁵Department of Pharmacology, Vascular Biology and Therapeutic Program, Yale School of Medicine, New Haven, CT, USA
^†These authors contributed equally: Shiyang Chen, Yajuan Zheng, Xiaojuan Ran
Correspondence: An Zeng(azeng@sibcb.ac.cn)Yi Arial Zeng(yzeng@sibcb.ac.cn)Jianfeng Chen(jfchen@sibcb.ac.cn)

Intestinal stem cell (ISC) differentiation is regulated precisely by a niche in the crypt, where lymphocytes may interact with stem and transient amplifying (TA) cells. However, whether and how lymphocyte–stem/TA cell contact affects ISC differentiation is largely unknown. Here, we uncover a novel role of T cell–stem/TA cell contact in ISC fate decisions. We show that intestinal lymphocyte depletion results in skewed ISC differentiation in mice, which can be rescued by T cell transfer. Mechanistically, integrin αEβ7 expressed on T cells binds to E-cadherin on ISCs and TA cells, triggering E-cadherin endocytosis and the consequent Wnt and Notch signaling alterations. Blocking αEβ7−E-cadherin adhesion suppresses Wnt signaling and promotes Notch signaling in ISCs and TA cells, leading to defective ISC differentiation. Thus, αEβ7+ T cells regulate ISC differentiation at single-cell level through cell–cell contact-mediated αEβ7−E-cadherin adhesion signaling, highlighting a critical role of the T cell–stem/TA cell contact in maintaining intestinal homeostasis.

https://doi.org/10.1038/s41422-021-00561-2

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