Xiaoliang Yu, Haikuo Ma, Bohan Li, Yuting Ji, Yayun Du, Siying Liu, Zhanhai Li, Yongjin Hao, Sheng Tian, Cong Zhao, Qian Du, Zhongqin Jin, Xueming Zhu, Yuanyuan Tian, Xin Chen, Xue Sun, Chengkui Yang, Fang Zhu, Jie Ju, Yunjing Zheng, Wei Zhang, Jingrui Wang, Tao Yang, Xinhui Wang, Jingjing Li, Xiangping Xu, Shujing Du, Haohao Lu, Feng Ma, Haibing Zhang, Yi Zhang, Xiaohu Zhang, Shaoyan Hu, Sudan He
Intestinal epithelial cells (IECs) are implicated in the propagation of T cell-mediated inflammatory diseases including graft-versus-host disease (GVHD), but the underlying mechanism remains poorly defined. Here, we report that IECs require receptor-interacting protein kinase-3 (RIPK3) to drive both gastrointestinal (GI) tract and systemic GVHD following allogeneic hematopoietic stem cell transplantation. Selectively inhibiting RIPK3 in IECs markedly reduces GVHD in murine intestine and liver. IEC RIPK3 cooperates with RIPK1 to trigger MLKL-independent production of T cell-recruiting chemokines and MHC class II molecules which amplify and sustain alloreactive T cell responses...
November 10, 2022: Blood