Go Against the Flow

Science Signaling  04 Oct 2011:
Vol. 4, Issue 193, pp. ec281
DOI: 10.1126/scisignal.4193ec281

Cells of our immune system continuously circulate through the blood and lymphoid tissues, maintaining a constant vigil against infections. Exit and entry between blood and tissues, and cell migration within tissues, is a highly regulated process, controlled by chemokine gradients. However, sometimes lymphocytes move against a chemokine gradient. Arnon et al. used a genetic approach to show that the G protein–coupled receptor kinase-2 (GRK2) is critical for down-regulating lymphocyte expression of S1P receptor-1 (S1PR1), the receptor for the lipid mediator sphingosine 1-phosphate (S1P). GRK2-mediated down-regulation of S1PR1 expression allows T cells to ignore high concentrations of S1P in the blood and to move into lymph nodes, and it also allows B cells to move between different cellular niches in the spleen to promote optimal access to antigens.

T. I. Arnon, Y. Xu, C. Lo, T. Pham, J. An, S. Coughlin, G. W. Dorn, J. G. Cyster, GRK2-dependent S1PR1 desensitization is required for lymphocytes to overcome their attraction to blood. Science 333, 1898–1903 (2011). [Abstract] [Full Text]