Group 3 innate lymphoid cells(ILC3s)control tissue homeostasis and orchestrate mucosal inflammation;however,the precise mechanisms governing ILC3 activity are fully understood.Here,we identified the transmembrane prot...Group 3 innate lymphoid cells(ILC3s)control tissue homeostasis and orchestrate mucosal inflammation;however,the precise mechanisms governing ILC3 activity are fully understood.Here,we identified the transmembrane protein neuropilin-1(NRP1)as a positive regulator of interleukin(IL)-17-producing ILC3s in the intestine.NRP1 was markedly upregulated in intestinal mucosal biopsies from patients with inflammatory bowel disease(IBD)compared with healthy controls.Genetic deficiency of NRP1 reduces the frequency of ILC3s in the gut and impairs their production of IL-17A in an NF-κB signaling-dependent and cell-intrinsic manner.The diminished IL-17A production in ILC3s altered the composition of the microbiota and improved the outcome of dextran sodium sulfate(DSS)-induced colitis.Furthermore,pharmacological inhibition of NRP1 with EG00229 alleviated the severity of colitis.These observations demonstrated the critical role of NRP1 in the control of intestinal ILC3s,suggesting that NRP1 is a potential therapeutic target for IBD.展开更多
基金upported by the following grants:National Natural Science Foundation of China(No.81925018,82130049,82430055,to J.Z.82321001 to Y.Y.,and 82225015 to Q.L.)+1 种基金supported by the National Key Research and Development Project of China(2021ZD0202400,to Q.L.)the New Cornerstone Science Foundation through the XPLORER PRIZE(to Q.L.).
文摘Group 3 innate lymphoid cells(ILC3s)control tissue homeostasis and orchestrate mucosal inflammation;however,the precise mechanisms governing ILC3 activity are fully understood.Here,we identified the transmembrane protein neuropilin-1(NRP1)as a positive regulator of interleukin(IL)-17-producing ILC3s in the intestine.NRP1 was markedly upregulated in intestinal mucosal biopsies from patients with inflammatory bowel disease(IBD)compared with healthy controls.Genetic deficiency of NRP1 reduces the frequency of ILC3s in the gut and impairs their production of IL-17A in an NF-κB signaling-dependent and cell-intrinsic manner.The diminished IL-17A production in ILC3s altered the composition of the microbiota and improved the outcome of dextran sodium sulfate(DSS)-induced colitis.Furthermore,pharmacological inhibition of NRP1 with EG00229 alleviated the severity of colitis.These observations demonstrated the critical role of NRP1 in the control of intestinal ILC3s,suggesting that NRP1 is a potential therapeutic target for IBD.
