title: IL-21R signaling suppresses IL-17+ gamma delta T cell responses and production of IL-17 related cytokines in the lung at steady state and after Influenza A virus infection.
abstract: Influenza A virus (IAV) infection of the respiratory tract elicits a robust immune response, which is required for efficient virus clearance but at the same time can contribute to lung damage and enhanced morbidity. IL-21 is a member of the type I cytokine family and has many different immune-modulatory functions during acute and chronic virus infections, although its role in IAV infection has not been fully evaluated. In this report we evaluated the contributions of IL-21/IL-21 receptor (IL-21R) signaling to host defense in a mouse model of primary IAV infection using IL-21R knock out (KO) mice. We found that lack of IL-21R signaling had no significant impact on virus clearance, adaptive T cell responses, or myeloid cell accumulations in the respiratory tract. However, a subset of inflammatory cytokines were elevated in the bronchoalveolar lavage fluid of IL-21R KO mice, including IL-17. Although there was only a small increase in Th17 cells in the lungs of IL-21R KO mice, we observed a dramatic increase in gamma delta (γδ) T cells capable of producing IL-17 both after IAV infection and at steady state in the respiratory tract. Finally, we found that IL-21R signaling suppressed the accumulation of IL-17+ γδ T cells in the respiratory tract intrinsically. Thus, our study reveals a previously unrecognized role of IL-21R signaling in regulating IL-17 production by γδ T cells.
authors: The Beirne B. Carter Center for Immunology Research, The University of Virginia, Charlottesville, Virginia, United States of America; Department of Pharmacology, The University of Virginia, Charlottesville, Virginia, United States of America.
authors: Emily K
authors: EK
authors: Moser
authors: Herman B. Wells Center for Pediatrics, The University of Indiana, Indianapolis, Indiana, United States of America.
authors: Jie
authors: J
authors: Sun
authors: The Beirne B. Carter Center for Immunology Research, The University of Virginia, Charlottesville, Virginia, United States of America; Department of Pathology, The University of Virginia, Charlottesville, Virginia, United States of America.
authors: Taeg S
authors: TS
authors: Kim
authors: The Beirne B. Carter Center for Immunology Research, The University of Virginia, Charlottesville, Virginia, United States of America; Department of Pathology, The University of Virginia, Charlottesville, Virginia, United States of America.
authors: Thomas J
authors: TJ
authors: Braciale
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D009980:Influenza A virus / Q000276:immunology / Q000472:pathogenicity*; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000821:virology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000378:metabolism*; D053655:Receptors, Interleukin-21 / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D016207:Cytokines; D020381:Interleukin-17; D012333:RNA, Messenger; D016692:Receptors, Antigen, T-Cell, gamma-delta; D053655:Receptors, Interleukin-21