IL-33 induces immunosuppressive neutrophils via a type 2 innate lymphoid cell/IL-13/STAT6 axis and protects the liver against injury in LCMV infection-induced viral hepatitis
作者机构：Department of Microbiology and ImmunologyUniversity of Texas Medical BranchGalvestonTX 77555-1070USA Department of Infectious DiseasesKey Laboratory of Viral Hepatitis of HunanXiangya HospitalCentral South UniversityChangsha 410008China Pathology and Institute for Human Infections and ImmunityUniversity of Texas Medical BranchGalvestonTX 77555-1070USA
出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)
年 卷 期：2019年第16卷第2期
页 面：126-137页
核心收录：
学科分类：0710[理学-生物学] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学]
基 金：in part,by grants from the NIH(AI109100 and AI126371 to JS) PY was a visiting scientist partially supported by the Department of Infectious Diseases,Xiangya Hospital,China and the Natural Science Foundation of Hunan Province(no.14JJ6003) DMKY and ZK were recipients of summer internships from an NIAID T35 training grant(AI078878,PI:LS).
主 题：IL-33 ILC2 neutrophils viral infection liver
摘 要：Viral hepatitis is still a public health problem affecting several million people around the world.Neutrophils are polymorphonuclear cells that have a critical role in antibacterial infection.However,the role of neutrophils in viral infection is not fully understood.By using a mouse model of lymphocytic choriomeningitis virus infection-induced viral hepatitis,we observed increased neutrophil recruitment in the liver accompanied by enhanced CD8+T-cell responses.Liver neutrophils expressed high levels of immunomodulatory cytokines,such as C-X-C chemokine ligand 2,arginase-1,inducible nitric oxide synthase and interleukin(IL)-10,demonstrating immunosuppressive properties.Depletion of neutrophils in vivo by a neutralizing antibody resulted in the exacerbation of liver injury and the promotion of T-cell responses at the immune contraction stage.IL-33 significantly induced neutrophil recruitment in the liver and attenuated liver injury by limiting effector T-cell accumulation.Mechanistically,we found that IL-33 promoted the expression of arginase-1 in neutrophils through the type 2 innate lymphoid cell(ILC2)-derived IL-13.Additionally,IL-13 increased the inhibitory effect of neutrophils on CD8+T-cell proliferation in vitro,partially through arginase-1.Finally,we found that IL-13 induced arginase-1 expression,depending on signal transducer and activator of transcription factor 6(STAT6)signaling.Therefore,IL-33 induced immunosuppressive neutrophils via an ILC2/IL-13/STAT6 axis.Collectively,our findings shed new light on the mechanisms associated with IL-33-triggered neutrophils in the liver and suggest potential targets for therapeutic investigation in viral hepatitis.
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