CCR6 regulates the function of alloreactive and regulatory CD4+ T cells during acute graft-versus-host disease.

The chemokine receptor CCR6 is expressed by CD4+ T cell effector/memory and regulatory effector/memory (TREM) subsets. Here we show that CCR6 modulates graft-versus-host-disease (GVHD) responses in both alloreactive CD4+ T effector cells and regulatory T (Treg) cells. Mortality and morbidity due to acute GVHD were drastically reduced and delayed when naïve T cells were derived from CCR6-deficient donor mice.

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 histocompatibility 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.

CCR6 has a non-redundant role in the development of inflammatory bowel disease.

Antigen-loaded tissues such as the intestinal mucosa must simultaneously elicit appropriate immune response to innocuous bacteria and food proteins, and to potentially harmful antigens. Impairment of the mechanisms controlling this response may mediate the excessive immune reaction that can lead to tissue destruction and inflammatory intestinal diseases, including inflammatory bowel disease. The intestinal epithelium influences local immune responses through the expression of adhesion molecules, costimulatory factors, cytokines and chemokines.