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

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  • 作者：Chen Shiyang, Zheng Yajuan, Ran Xiaojuan, Du Hui, Feng Hua, Yang Lei, Wen Yating, Lin Changdong, Wang Shihui, Huang Mengwen, Yan Zhanjun, Wu Dianqing, Wang Hongyan, Ge Gaoxiang, Zeng An, Zeng Yi Arial, Chen Jianfeng
  • 期刊：CELL RESEARCH
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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.

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