C-C chemokine receptor type 9 (CCR9) (CCR9)

C-C chemokine receptor type 9 (CCR9) is a G protein-coupled receptor (GPCR) that serves as a key regulator of lymphocyte trafficking and development [1, 2, 6]. It is primarily expressed on thymocytes and a subset of memory T cells, where it mediates homing to the small intestine by binding to its specific ligand, CCL25 (also known as TECK) [6, 10, 15]. The CCR9-CCL25 axis is essential for maintaining immune homeostasis in the gut but becomes dysregulated in various inflammatory and neoplastic diseases [3, 7, 13]. In inflammatory bowel diseases (IBD), such as Crohn's disease and ulcerative colitis, CCR9 facilitates the recruitment of pro-inflammatory leukocytes to the intestinal mucosa, contributing to chronic inflammation [5, 7, 13]. Furthermore, CCR9 is frequently overexpressed in T-cell acute lymphoblastic leukemia (T-ALL) and certain solid tumors like melanoma, where it promotes cell survival, chemoresistance, and metastasis to the small intestine [1, 2, 9, 16]. Therapeutic interventions targeting this receptor include small-molecule antagonists like vercirnon (CCX282-B) designed to block lymphocyte infiltration in IBD and novel CAR-T cell therapies aimed at treating CCR9-positive malignancies [5, 7, 9]. Despite its potential, clinical trials for CCR9 antagonists in IBD have yielded mixed results, highlighting the complexity of chemokine signaling in different disease contexts [5, 8].

Other names

CD199GPR-9-6CC-CKR-9GPR28C-C motif chemokine receptor 9

CCR9 antagonism, which inhibits the binding of the ligand CCL25 and prevents the chemotaxis and homing of CCR9-expressing lymphocytes to the gut or tumor sites [7, 13]. Additionally, CAR-T cell therapies target CCR9-expressing cells for direct cytotoxic elimination [9].