Type 3 innate lymphoid cell-derived lymphotoxin prevents microbiota-dependent inflammation  

作　　者：Yuan Zhang Tae-Jin Kim Joanna A Wroblewska Vera Tesic Vaibhav Upadhyay Ralph R Weichselbaum Alexei V Tumanov Hong Tang Xiaohuan Guo Haidong Tang Yang-Xin Fu 

机构地区：[1]Department of Pathology,University of Chicago,Chicago,IL 60637,USA [2]Department of Biochemistry and Molecular Biology,Korea University College of Medicine,Seoul 02841,Korea [3]Committee on Immunology,Department of Pathology,University of Chicago,Chicago,IL 60637,USA [4]Department of Radiation and Cellular Oncology and The Ludwig Center for Metastasis Research,University of Chicago,Chicago,IL 60637,USA [5]Department of Microbiology,Immunology and Molecular Genetics,University of Texas Health Science Center San Antonio,San Antonio,TX 78229,USA [6]Chinese Academy of Sciences Key Laboratory for Infection and Immunity,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China [7]Institute of Immunology,Tsinghua University School of Medicine,Beijing 100084,China [8]Department of Pathology,University of Texas Southwestern Medical Center,Dallas,TX 75390,USA

出　　处：《Cellular & Molecular Immunology》2018年第7期697-709,共13页中国免疫学杂志（英文版）

摘　　要：Splenomegaly is a well-known phenomenon typically associated with inflammation.However,the underlying cause of this phenotype has not been well characterized.Furthermore,the splenomegaly phenotype seen in lymphotoxin(LT)signaling-deficient mice is characterized by increased numbers of splenocytes and splenic neutrophils.Splenomegaly,as well as the related phenotype of increased lymphocyte counts in non-lymphoid tissues,is thought to result from the absence of secondary lymphoid tissues in LT-deficient mice.We now present evidence that mice deficient in LTα1β2 or LTβR develop splenomegaly and increased numbers of lymphocytes in non-lymphoid tissues in a microbiota-dependent manner.Antibiotic administration to LTα1β2-or LTβR-deficient mice reduces splenomegaly.Furthermore,re-derived germ-free Ltbr−/−mice do not exhibit splenomegaly or increased inflammation in non-lymphoid tissues compared to specific pathogen-free Ltbr−/−mice.By using various LTβ-and LTβR-conditional knockout mice,we demonstrate that retinoic acid-related orphan receptorγT-positive type 3 innate lymphoid cells provide the required active LT signaling to prevent the development of splenomegaly.Thus,this study demonstrates the importance of LT-mediated immune responses for the prevention of splenomegaly and systemic inflammation induced by microbiota.

关 键 词：GERM-FREE LYMPHOTOXIN MICROBIOTA SPLENOMEGALY type 3 innate lymphoid cells 

分 类 号：R73[医药卫生—肿瘤]