{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CCR6 functions as a key chemokine receptor expressed predominantly on interleukin‐17–producing T helper cells and related lymphocyte subsets, thereby serving both as a cellular marker and as a mediator of directed migration. Human Th17 cells—including subsets that co‐produce interferon‐γ or that derive from regulatory T cells—selectively express CCR6, which facilitates their recruitment into inflamed tissues and mucosal sites via its binding to the ligand CCL20, constitutively produced by epithelial cells in structures such as the choroid plexus and inflamed synovium."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In experimental autoimmune encephalomyelitis, for example, deficiency of CCR6 disrupts early T‐cell entry into the central nervous system, thereby preventing the cascade of inflammatory cell recruitment."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Similarly, in rheumatoid arthritis, the CCR6–CCL20 axis is implicated in the accumulation of arthritogenic Th17 cells in the joints—a process that is further reinforced by the autocrine production of CCL20 by Th17 cells, ultimately sustaining local inflammation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In autoimmune settings, CCR6 is also expressed on regulatory T cells, and its engagement can influence the migration of both pathogenic and regulatory subsets to inflammatory sites, thereby modulating disease severity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Furthermore, innate lymphocyte populations, such as IL-17–producing γδ T cells, express CCR6, highlighting its broader role in orchestrating early immune responses at barrier surfaces."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In human skin, resident memory T cells display high levels of CCR6 along with other homing receptors, which may underlie their rapid recruitment in inflammatory disorders such as psoriasis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", and increased CCR6 expression is a consistent feature of IL-17–producing cells in both blood and tissue."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Moreover, in tumor microenvironments, intratumoral Th17 cells often exhibit elevated CCR6 expression, which may contribute to enhanced local inflammation and angiogenesis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ", while Th17 cytokines can further amplify CCL20 production, setting up a positive chemotactic feedback loop that perpetuates tissue inflammation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Francesco Annunziato, Lorenzo Cosmi, Veronica Santarlasci, et al. 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