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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 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

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Infectious, atopic and inflammatory diseases, childhood adversities and familial aggregation are independently associated with the risk for mental disorders: Results from a large Swiss epidemiological study

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World Journal of Psychiatry 2016年第4期6卷 419-430页

作者： Vladeta Ajdacic-Gross Aleksandra Aleksandrowicz Stephanie Rodgers Margot Mutsch Anja tesic Mario Müller Wolfram Kawohl Wulf R?ssler Erich Seifritz Enrique Castelao Marie-Pierre F Strippoli Caroline Vandeleur Roland von K?nel Rosa Paolicelli Markus A Landolt Cornelia Witthauer Roselind Lieb Martin Preisig Department of Psychiatry Psychotherapy and Psychosomatics Psychiatric Hospital University of Zurich Epidemiology Biostatistics and Prevention Institute University of Zurich Department of Psychiatry University Hospital of Lausanne Department of Neurology Bern University Hospital Clinic Barmelweid Division of Psychiatry Research University of Zurich University Children’s Hospital Zurich and Children’s Research Center and Division of Child and Adolescent Health Psychology Department of Psychology University of Zurich Department of Psychology Division of Clinical Psychology and Epidemiology University of Basel

AIM To examine the associations between mental disorders and infectious, atopic, inflammatory diseases while adjusting for other risk factors.METHODS We used data from PsyC oL aus, a large Swiss Population Cohort Study(n = 3720; age range 35-66). Lifetime diagnoses of mental disorders were grouped into the following categories: Neurodevelopmental, anxiety(early and late onset), mood and substance disorders. They were regressed on infectious, atopic and other inflammatory diseases adjusting for sex, educational level, familial aggregation, childhood adversities and traumatic experiences in childhood. A multivariate logistic regression was applied to each group of disorders. In a complementary analysis interactions with sex were introduced via nested effects. RESULTS Associations with infectious, atopic and other chronic inflammatory diseases were observable together with consistent effects of childhood adversities and familial aggregation, and less consistent effects of trauma in each group of mental disorders. Streptococcal infections were associated with neurodevelopmental disorders(men), and measles/mumps/rubella-infections with early and late anxiety disorders(women). Gastric inflammatory diseases took effect in mood disorders(both sexes) and in early disorders(men). Similarly, irritable bowel syndrome was prominent in a sex-specific way in mood disorders in women, and, moreover, was associated with early and late anxiety disorders. Atopic diseases were associated with late anxiety disorders. Acne(associations with mood disorders in men) and psoriasis(associations with early anxiety disorders in men and mood disorders in women) contributed sex-specific results. Urinary tract infections were associated with mood disorders and, in addition, in a sex-specific way with late anxiety disorders(men), and neurodevelopmental and early anxiety disorders(women).CONCLUSION Infectious, atopic and inflammatory diseases areimportant risk factors for all groups of mental disorders. The sexual dimorphism of the associations is

关键词： Neurodevelopmental disorders Mental disorders Substance abuse Childhood diseases Infectious diseases Atopic diseases Chronic inflammatory diseases Risk factors

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