{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CCR9 is a CC chemokine receptor that plays a critical role in directing immune cells to the gut. Its only known ligand, thymus‐expressed chemokine (TECK/CCL25) (see"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ", stimulates the migration of specific leukocyte subsets. Activated T lymphocytes imprinted by Peyer’s patch dendritic cells express high levels of CCR9 along with integrin α4β7, thereby acquiring a gut‐homing phenotype that enables them to localize efficiently to the small intestine."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, CD103⁺ dendritic cells from both the small intestinal lamina propria and mesenteric lymph nodes promote the induction of CCR9 on responding T cells"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", distinguishing these antigen‐presenting cells from their CD103⁻ counterparts that instead favor other T‐cell effector functions."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its role in establishing gut tropism in activated T cells, CCR9 mediates the recruitment of specific lymphocyte populations to the intestinal epithelium. For example, naive α(E)β7⁺ CD8⁺ T cells and a subset of recently activated CD8⁺ lymphocytes selectively maintain CCR9 expression, which is essential for their migration into the small-intestinal mucosa."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Similarly, plasmacytoid dendritic cells (pDCs) exhibit high levels of CCR9, which are pivotal for their homing under both steady-state and inflammatory conditions; CCR9-deficient animals display a marked reduction in intestinal pDC numbers."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n During development, CCR9 also contributes to the early colonization of the thymus by T-lymphoid progenitors in conjunction with other receptors such as CCR7; mice that are deficient in both receptors display impaired prevascular thymus seeding."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Furthermore, perturbations in CCR9 signaling have been linked to dysregulated intestinal immune responses. For instance, in settings where vitamin D receptor deficiency leads to decreased CCR9 expression on T cells, critical intraepithelial lymphocyte populations (e.g. CD8αα IELs) fail to home properly, thereby contributing to an enhanced inflammatory response."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In a murine model of colitis, disruption of the CCL25/CCR9 axis not only exacerbated inflammation in the large intestine but also altered dendritic cell subset distribution and cytokine production."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings establish that the CCL25/CCR9 axis is essential for regulating the trafficking, localization, and functional responses of multiple immune cell types in the gut. By mediating the migration of T cells, pDCs, and other leukocyte subsets, CCR9 ensures proper mucosal immune surveillance and homeostasis, while its disruption can contribute to aberrant immune responses and inflammatory diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "A Zaballos, J Gutiérrez, R Varona, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cutting edge: identification of the orphan chemokine receptor GPR-9-6 as CCR9, the receptor for the chemokine TECK."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (1999)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "10229797"}], "href": "https://pubmed.ncbi.nlm.nih.gov/10229797"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "J Rodrigo Mora, Maria Rosa Bono, N Manjunath, et al. 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