Ccr6, a G protein-coupled receptor, is expressed on various cells such as B cells, immature dendritic cells, innate lymphoid cells, regulatory CD4 T cells, and Th17 cells [1,3,6,9]. It binds to its sole ligand CCL20, forming a signaling network that is implicated in multiple biological processes including immune homeostasis, activation, and leukocyte migration during inflammation [1,2,3,5,6,7,8,9]. This CCR6-CCL20 axis is crucial in various diseases like autoimmune diseases, cancers, and inflammatory diseases [1,2,3,5].

In colitis-associated carcinoma, loss of SMAD4 in mouse colon epithelium leads to increased CCL20 expression and recruitment of CCR6+ immune cells such as T regulatory, Th17, and dendritic cells, contributing to tumorigenesis. However, loss of CCR6 abrogates these immune responses and reduces the incidence of colitis-associated tumors [4]. In psoriasis, IL-17A-producing immune cells stimulate epidermal keratinocytes to produce CCL20, which recruits CCR6+ Th17 cells into lesional skin, creating an IL-17A-rich cutaneous milieu [5]. In human chronic pancreatitis, single-cell sequencing shows distinct immune characteristics with significantly enriched CCR6+ CD4+ T cells and up-regulation of CCL20 among monocytes in hereditary CP, suggesting the CCR6-CCL20 axis as a potential target [7].

In conclusion, Ccr6, through its interaction with CCL20, plays essential roles in immune-related biological processes and is involved in the pathogenesis of multiple diseases. Gene knockout models, such as the CCR6 knockout mice, have revealed its significance in colitis-associated carcinoma, psoriasis, and chronic pancreatitis, providing insights into disease mechanisms and potential therapeutic targets.