title: RGS16 attenuates pulmonary Th2/Th17 inflammatory responses.
abstract: The regulators of G protein signaling (RGS) protein superfamily negatively controls G protein-coupled receptor signal transduction pathways. RGS16 is enriched in activated/effector T lymphocytes. In this paper, we show that RGS16 constrains pulmonary inflammation by regulating chemokine-induced T cell trafficking in response to challenge with Schistosoma mansoni. Naive Rgs16(-/-) mice were "primed" for inflammation by accumulation of CCR10(+) T cells in the lung. Upon pathogen exposure, these mice developed more robust granulomatous lung fibrosis than wild-type counterparts. Distinct Th2 or putative Th17 subsets expressing CCR4 or CCR10 accumulated more rapidly in Rgs16(-/-) lungs following challenge and produced proinflammatory cytokines IL-13 and IL-17B. CCR4(+)Rgs16(-/-) Th2 cells migrated excessively to CCL17 and localized aberrantly in challenged lungs. T lymphocytes were partially excluded from lung granulomas in Rgs16(-/-) mice, instead forming peribronchial/perivascular aggregates. Thus, RGS16-mediated confinement of T cells to Schistosome granulomas mitigates widespread cytokine-mediated pulmonary inflammation.
authors.affiliation: Molecular Signal Transduction Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Sucharita P
authors.initials: SP
authors.lastname: Shankar
authors.forename: Mark S
authors.initials: MS
authors.lastname: Wilson
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: DiVietro
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Mentink-Kane
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Xie
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Wynn
authors.forename: Kirk M
authors.initials: KM
authors.lastname: Druey
mesh_terms: D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005434:Flow Cytometry; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011014:Pneumonia / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D020710:RGS Proteins / Q000276:immunology* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D020710:RGS Proteins; C107413:RGS16 protein