Publication from Wei XU lab, The journal of Immunology

On November 20th, 2019, researchers at Dr. Xu’s groups published an article entitled “Pathogenic Role of an IL-23/γδT17/Neutrophil Axis in Coxsackievirus B3-Induced Pancreatitis.” in The journal of Immunology.


Coxsackievirus B is a common cause of viral myocarditis and pancreatitis. IL-17A is intensively involved in the pathogenesis of viral myocarditis. Whether IL-17A plays a role in Coxsackievirus B-induced pancreatitis, characterized by acinar cell destruction and immune infiltration, remains largely unknown. We found a significant, but transient, increase of IL-17A expression and γδT influx in the pancreas of C57BL/6J mice within 3 d following CVB3 infection. The pancreatic IL-17A was mainly produced by Vγ4 γδ T cells, to a lesser extent by CD4+ Th17 cells. IL-17A-/- and TCRδ-/- mice both reduced their susceptibility to CVB3 infection and pancreatitis severity when compared with the wild-type mice, without altering viral load. mAb depletion of Vγ4γδ T cells significantly improved mice survival and pancreatic pathology via decreasing Th17 expansion and neutrophil influx into the pancreas compared with isotype-treated mice. Transfer of Vγ4γδ T cells from wild-type, but not IL-17-/-, mice reconstituted TCRδ-/- mice to produce IL-17 and develop pancreatitis to the level of wild-type mice during CVB3 infection, indicating γδ T IL-17A is required for the onset of viral pancreatitis. IL-23 was robustly induced in the pancreas within the first day of infection. Administration of exogenous rIL-23 to mice increased CVB3 pancreatitis through in vivo expansion of IL-17+γδT17 cells at 12 h postinfection. Our findings reveal a key pathogenic role for early-activated γδT17 cells in viral pancreatitis via promoting neutrophil infiltration and Th17 induction. This IL-23/γδT17/neutrophil axis is critically involved in the onset of CVB3 pancreatitis and represents a potential treating target for the disease.


Kepeng Yan is the first author. Jie Yang, Qian Qian, Dan Xu etc. are contributing authors. Prof. Wei Xu is the corresponding author. This work was supported by National Natural Science Foundation of China Grants (31870903 and 31670930), a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions, the Jiangsu Natural Science Foundation Monumental Project (14KJA310005), the Jiangsu Provincial Innovative Research Team, and Program for Changjiang Scholars and Innovative Research Team in University Grant PCSIRTIRT1075.