Cxcl17-/- mice develop exacerbated disease in a Tcell-dependent autoimmune model.

Abstract

CXCL17 is a homeostatic chemokine in the mucosa known to chemoattract dendritic cells and macrophages but can also be expressed elsewhere under inflammatory conditions. Cxcl17-/- mice have lower numbers of macrophages or dendritic cells in mucosal tissues. CXCL17 is also able to chemoattract suppressor myeloid cells that can recruit regulatory Tcells. To explore a possible role of Cxcl17 in Tcells, we studied Tcell populations from Cxcl17-/- or wild-type (WT) littermate mice. Cxcl17-/- mice have higher numbers of CD4+ and CD8+ Tcells in spleen and lymph nodes (LNs). Upon activation, they produce higher levels of several proinflammatory cytokines and chemokines. Furthermore, a Cxcl17-/- mouse developed exacerbated disease in a Tcell-dependent model of experimental autoimmune encephalomyelitis (EAE). By 18 days after immunization with myelin oligodendrocyte peptide, only 44% of Cxcl17-/- mice were still alive vs. 90% for WT mice. During EAE, Cxcl17-/- mice exhibited higher numbers of lymphoid and myeloid cells in spleen and LNs, whereas they had less myeloid cell infiltration in the CNS. Cxcl17-/- mice also had higher levels of some inflammatory cytokines in serum, suggesting that they may be involved in the poor survival of these mice. Abnormal Tcell function may reflect altered myeloid cell migration, or it could be due to altered Tcell development in the thymus. We conclude that CXCL17 is a novel factor regulating Tcell homeostasis and function.