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

Cellular & Molecular Immunology 2018年第7期15卷 697-709页

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 Department of Pathology University of ChicagoChicagoIL 60637USA Department of Biochemistry and Molecular Biology Korea University College of MedicineSeoul 02841Korea Committee on Immunology Department of PathologyUniversity of ChicagoChicagoIL 60637USA Department of Radiation and Cellular Oncology and The Ludwig Center for Metastasis Research University of ChicagoChicagoIL 60637USA Department of Microbiology Immunology and Molecular GeneticsUniversity of Texas Health Science Center San AntonioSan AntonioTX 78229USA Chinese Academy of Sciences Key Laboratory for Infection and Immunity Institute of BiophysicsChinese Academy of SciencesBeijing 100101China Institute of Immunology Tsinghua University School of MedicineBeijing 100084China Department of Pathology University of Texas Southwestern Medical CenterDallasTX 75390USA

Splenomegaly is a well-known phenomenon typically associated with ***,the underlying cause of this phenotype has not been well ***,the splenomegaly phenotype seen in lymphotoxin(LT)signaling-deficient mice is characterized by increased numbers of splenocytes and splenic ***,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 *** 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 *** administration to LTα1β2-or LTβR-deficient mice reduces ***,re-derived germ-free Ltbr−/−mice do not exhibit splenomegaly or increased inflammation in non-lymphoid tissues compared to specific pathogen-free Ltbr−/−*** 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 ***,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

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