The Role of RGS16 in T lymphocyte responses

Asthma is a Th2‐mediated inflammatory disease resulting from the cooperation of many cell types, receptors, and cellular events, many of which are caused by signal transduction through G Protein Coupled Receptors (GPCRs). Current therapies for asthma target GPCRs but prolonged use results in increased airway hyperreactivity and receptor desensitization. RGS (Regulator of G protein Signaling) proteins negatively regulate signaling through GPCRs by accelerating the rate of GTP hydrolysis of the α subunit of the heterotrimeric G protein. RGS 16 was originally identified as an IL‐2 responsive gene in human T cells. Th2 cytokine production is increased in transgenic mice expressing RGS16 in CD4 + and CD8 + T lymphocytes in a mouse model of allergic inflammation and trafficking of these cells to the lung is reduced. High RGS16 levels are found in germinal center T cells, and upregulation of RGS16 mRNA results in impaired migration towards CXCL12. RGS16 is hypothesized modulate T cell trafficking to the lung in response to inflammation. We are currently assessing the role of RGS16 in T cell responses. We have characterized RGS16 expression by intracellular flow cytometry. We have knocked down RGS16 expression in Jurkats and assessed effects on Ca 2+ mobilization, CD69 and T Cell Receptor (TCR) expression levels, intracellular localization by immunofluorescence and immunohistochemistry, and tyrosine phosphorylation levels. Preliminary results show no change in expression levels of the α/β TCR when RGS16 is knocked down, but higher phosphorylation levels of ZAP70 and ERK. Taken together, these results suggest that RGS16 has a negative effect on signaling through an activated TCR. Determination of a role for RGS16 in T cell responses may provide another mechanism by which therapeutics can be developed and administered in the treatment and control of asthma and allergic inflammation.