| Literature DB >> 34518654 |
Shiyang Chen1,2, Yajuan Zheng2, Xiaojuan Ran2, Hui Du2, Hua Feng3, Lei Yang2, Yating Wen2, Changdong Lin2, Shihui Wang2, Mengwen Huang2, Zhanjun Yan4, Dianqing Wu5, Hongyan Wang1,2, Gaoxiang Ge1,2, An Zeng6, Yi Arial Zeng7,8, Jianfeng Chen9,10.
Abstract
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.Entities:
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Year: 2021 PMID： 34518654 PMCID： PMC8648739 DOI： 10.1038/s41422-021-00561-2
Source DB: PubMed Journal: Cell Res ISSN： 1001-0602 Impact factor: 25.617