RGS3 controls T lymphocyte migration in a model of Th2-mediated airway inflammation

T cell migration toward sites of antigen exposure is mediated by G protein signaling and is a key function in the development of immune responses. Regulators of G protein signaling (RGS) proteins modulate G protein signaling; however, their role in the regulation of adaptive immune responses has not been thoroughly explored. Herein we demonstrated abundant expression of the G_i/G_q-specific RGS3 in activated T cells, and that diminished RGS3 expression in a T cell thymoma increased cytokine-induced migration. To examine the role of endogenous RGS3 in vivo, mice deficient in the RGS domain (RGS3 ^ΔRGS) were generated and tested in an experimental model of asthma. Compared with littermate controls, the inflammation in the RGS3 ^ΔRGS mice was characterized by increased T cell numbers and the striking development of perivascular lymphoid structures. Surprisingly, while innate inflammatory cells were also increased in the lungs of RGS3 ^ΔRGS mice, eosinophil numbers and Th2 cytokine production were equivalent to control mice. In contrast, T cell numbers in the draining lymph nodes (dLN) were reduced in the RGS3 ^{Delta; RGS}, demonstrating a redistribution of T cells from the dLN to the lungs via increased RGS3 ^ΔRGS T cell migration. Together these novel findings show a nonredundant role for endogenous RGS3 in controlling T cell migration in vitro and in an in vivo model of inflammation.