1. RGS16 Attenuates Pulmonary Th2/Thl7 Inflammatory Responses.
- Author
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Shankar, Sucharita P., Wilson, Mark S., DiVietro, Jeffrey A., Mentink-Kane, Margaret M., Zhihui Xie, Wynn, Thomas A., and Druey, Kirk M.
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CELLULAR signal transduction , *G protein coupled receptors , *T cells , *INFLAMMATION , *SCHISTOSOMA , *CYTOKINES , *GRANULOMA - Abstract
The regulators of Gprotein signaling (RGS) protein superfamily negatively controls Gprotein-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 Rgsl6-/- 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 Thl7 subsets expressing CCR4 or CCR10 accumulated more rapidly in Rgsl6-/- lungs following challenge and produced proinflammatory cytokines IL-13 and IL-17B. CCRA+Rgsl6-/- Th2 cells migrated excessively to CCL17 and localized aberrantly in challenged lungs. T lymphocytes were partially excluded from lung granulomas in Rgsl6-/- mice, instead forming peribronchial/perivascular aggregates. Thus, RGS16-mediated confinement of T cells to Schistosome granulomas mitigates widespread cytokine-mediated pulmonary inflammation. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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