Dendritic cell expression of the signaling molecule TRAF6 is required for immune tolerance in the lung.
Immune tolerance in the lung is important for preventing hypersensitivity, such as allergic asthma. Maintenance of tolerance in the lung is established by coordinated activities of poorly understood cellular and molecular mechanisms, including participation of dendritic cells (DCs). We have previously identified DC expression of the signaling molecule TRAF6 as a non-redundant requirement for the maintenance of immune tolerance in the small intestine of mice. Because mucosal tissues share similarities in how they interact with exogenous antigens, we examined the role of DC-expressed TRAF6 in the lung. As with the intestine, we found that the absence TRAF6 expression by DCs led to spontaneous generation of Th2-associated immune responses and increased susceptibility to model antigen-induced asthma. To examine the role of commensal microbiota, mice deficient in TRAF6 in DCs were treated with broad-spectrum antibiotics and/or re-derived on a germ-free (GF) background. Interestingly, we found that antibiotics-treated specific pathogen-free, but not GF, mice showed restored immune tolerance in the absence of DC-expressed TRAF6. We further found that antibiotics mediate microbiota-independent effects on lung T cells to promote immune tolerance in the lung. This work provides both a novel tool for studying immune tolerance in the lung and an advance in our conceptual understanding of potentially common molecular mechanisms of immune tolerance in both the intestine and the lung.
Academy of Immunology and Microbiology, Institute for Basic Science, Pohang 37666, Republic of Korea.|Department of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang 37666, Republic of Korea.
Daehee
D
Han
Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Matthew C
MC
Walsh
Academy of Immunology and Microbiology, Institute for Basic Science, Pohang 37666, Republic of Korea.|Department of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang 37666, Republic of Korea.
Kwang Soon
KS
Kim
Academy of Immunology and Microbiology, Institute for Basic Science, Pohang 37666, Republic of Korea.|Department of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang 37666, Republic of Korea.
Sung-Wook
SW
Hong
Academy of Immunology and Microbiology, Institute for Basic Science, Pohang 37666, Republic of Korea.|Department of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang 37666, Republic of Korea.
Junyoung
J
Lee
Academy of Immunology and Microbiology, Institute for Basic Science, Pohang 37666, Republic of Korea.|Department of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang 37666, Republic of Korea.
Jaeu
J
Yi
Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Gloriany
G
Rivas
Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Yongwon
Y
Choi
Academy of Immunology and Microbiology, Institute for Basic Science, Pohang 37666, Republic of Korea.|Department of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang 37666, Republic of Korea.|Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
Charles D
CD
Surh
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D001249:Asthma / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics; D018928:Immunity, Mucosal; D008168:Lung / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D064307:Microbiota / Q000276:immunology; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology*
D000900:Anti-Bacterial Agents; D048029:TNF Receptor-Associated Factor 6
Th2 immunity; antibiotics; asthma; dendritic cell; germ-free