CCR6 and CCL20: partners in intestinal immunity and lymphorganogenesis

The CCR6 chemokine receptor is expressed by most B cells and subsets of T cells and dendritic cells (DCs) found in the gut mucosal immune system. CCL20, the single chemokine ligand for CCR6, is selectively made by the follicle-associated epithelium (FAE) overlying Peyer's patches (PPs) and isolated lymphoid follicles (ILFs). CCL20 contributes to the recruitment of CCR6-expressing B cells to these structures. CCL20 expression by the intestinal epithelium is also highly inducible in response to inflammatory stimuli. Thus, CCL20 functions as both an inflammatory and homeostatic chemokine. Interactions between CCR6 and CCL20 play a role at several stages in the development of intestinal lymphoid structures. A subset of the c-kit(+) lymphoid precursors found in cryptopatches (CPs) expresses CCR6. Recruitment of B cells to CPs and the subsequent expansion and organization of these B cells allows differentiation of some of these structures into ILFs. In CCR6 knockout mice, PPs are smaller with fewer follicles and the development of ILFs is compromised. These defects in the development of mucosal inductive sites in CCR6-deficient mice are responsible for decreased IgA production to oral antigens. CCR6 can be included with CXCR5 and CCR7 in a list of chemokine receptors that participate in shaping the organized lymphoid structures that are part of the intestinal immune system.