Abstract: Cytohesin binder and regulator (Cybr) is known to regulate leukocyte adhesion and migration. However, its function in T-cells is poorly understood. Here, we investigated the role of Cybr in CD4+ T-cell function and host immunity. Cybr inhibited p38 phosphorylation following CD4+ T-cell stimulation. Since p38 regulates the expression of T-box expressed in T-cells (T-bet) but not GATA binding protein 3 (GATA-3) in T-cells, Cybr decreased the expression of T-bet and IFN-γ in CD4+ T-cells. Moreover, we found that host immunity against Listeria infection and IFN-γ production in blood were significantly compromised in Cybr-overexpressing transgenic mice. In summary, our data suggest that Cybr represses the expression of T-bet and IFN-γ via an inhibition of p38 in T-cells and consequently reduces host resistance to bacterial infection in mice.