Ccr9, a G protein-coupled receptor, is expressed on several immune cells like dendritic cells, CD4+ T cells, and B cells [3]. It binds to its exclusive ligand CCL25, with CCL25 mostly produced by gut and thymic epithelial cells. Ccr9 is crucial in driving immune cell migration towards CCL25 gradients, playing a role in processes like immune cell homing to the gut mucosa and thymus [3]. It is also involved in various signaling pathways, especially those related to tumor chemoresistance, metastasis, and inflammation [1,2,4]. Gene knockout mouse models have been valuable in understanding its physiological functions [2].

Early research on Ccr9-deficient mouse models confirmed its functions in inflammatory responses [2]. In the context of diseases, Ccr9 and CCL25 are overexpressed in many malignant tumors, closely associated with tumor proliferation, apoptosis, invasion, migration, and drug resistance [1]. In T-cell acute lymphoblastic leukemia (T-ALL), overexpression of Ccr9 promotes disease progression by enhancing cholesterol biosynthesis [8]. In inflammatory bowel disease (IBD), Ccr9 is a key molecule in leukocyte homing to gut mucosa, and its antagonists have shown potential in retarding disease progression [5,6]. In adriamycin-induced cardiomyopathy, Ccr9 overexpression aggravates cardiac dysfunction, while knockdown alleviates the harmful effects [7].

In summary, Ccr9 is essential in immune cell migration and inflammation-related processes. Model-based research, especially Ccr9-deficient mouse models, has revealed its significant roles in multiple disease areas, including cancer, IBD, and cardiomyopathy. Understanding Ccr9 provides insights into disease mechanisms and potential therapeutic targets for these diseases.