CCR2 Regulates the Immune Response by Modulating the Interconversion and Function of Effector and Regulatory T Cells

Chemokinesand chemokine receptorsestablish a complex network modulating immune cell migration and localization. These molecules were also suggested to mediate the differentiation of leukocytes; however, their intrinsic, direct regulation of lymphocyte fate remained unclear. CCR2is the main chemokine receptorinducing macrophage and monocyte recruitment to sites of inflammation, and it is also expressed on T cells. To assess whether CCR2directly regulates T cellresponses, we followed the fates of CCR2−/− T cellsin T cell–specific inflammatory models. Our in vitro and in vivo results show that CCR2intrinsically mediates the expression of inflammatory T cellcytokines, and its absence on T cellsresults in attenuated colitis progression. Moreover, CCR2deficiency in T cellspromoted a program inducing the accumulation of Foxp3+ regulatory T cells, while decreasing the levels of Th17 cells in vivo, indicating that CCR2regulates the immune response by modulating the effector/regulatory T ratio.