CCR6 regulates CD4+ T-cell-mediated acute graft-versus-host disease responses

We studied the role of chemokine receptor CCR6 in acute graft-versus-host disease (GvHD), a pathology in which activated, host antigen-specific donor T cells selectively damage tissues such as skin, liver, and gut. GvHD incidence was reduced in major histocompatibility complex (MHC) class II-mismatched recipients of CD4(+) T cells from CCR6-deficient donors. In MHC-matched/minor histocom-patibility antigen-mismatched recipients of CD4(+)CD45RB(high) T cells from CCR6-deficient donors, infiltration of CD45(+) and CD4(+) cells to skin and gut, as well as lesion onset, were significantly delayed, and pathologic symptoms were milder. Consistent with this, in skin and gut of recipients of naive T cells from CCR6-deficient donors we observed lower levels of interferon gamma (IFN-gamma), interleukin 10 (IL-10), and the chemokines that control activated T-cell homing. We suggest a role for CCR6 in recruiting alloreactive CD4(+) T cells to target tissues and identify CCR6 as a potential therapeutic target for GvHD.