CXCR3, a chemokine receptor, binds to three ligands: CXCL9, CXCL10, and CXCL11 [2]. It plays a central role in cellular inflammation, involved in protective responses to pathogens and pathological conditions related to autoimmunity [3]. CXCR3 is highly expressed on innate and adaptive lymphocytes, as well as on various cell subsets in non-immune organs and tissues [3]. It is also associated with diseases like cancer, central nervous system diseases, and immune disorders [4]. Genetic models, such as gene knockout (KO) mouse models, can be used to study its function.

In cancer, genetic ablation of CXCR3 in regulatory T (Treg) cells disrupted the interactions between Treg cells and type I dendritic cells (DCs) in tumors [1]. This led to increased DC-CD8+ T cell interactions, enhanced tumor antigen-specific cross-presentation by DC1s, and increased CD8+ T cell priming and reactivation in tumors, ultimately impairing tumor progression [1]. In addition, CXCR3+ Treg cells in tumors exhibited an activated phenotype and interacted preferentially with CXCL9-producing BATF3+ DCs [1].

In conclusion, CXCR3 is crucial for Treg cell accumulation and immune suppression in tumors as revealed by KO mouse models [1]. It also plays a role in directing the biological properties of T cells in the context of cancer and autoimmunity, and in the generation of cellular inflammation in various diseases [2,3]. Understanding CXCR3 through model-based research provides insights into disease mechanisms and potential therapeutic targets.

References:

1. Moreno Ayala, Mariela A, Campbell, Timothy F, Zhang, Chenyu, Sher, Theo, DuPage, Michel. 2023. CXCR3 expression in regulatory T cells drives interactions with type I dendritic cells in tumors to restrict CD8+ T cell antitumor immunity. In Immunity, 56, 1613-1630.e5. doi:10.1016/j.immuni.2023.06.003. https://pubmed.ncbi.nlm.nih.gov/37392735/

2. Karin, Nathan. 2020. CXCR3 Ligands in Cancer and Autoimmunity, Chemoattraction of Effector T Cells, and Beyond. In Frontiers in immunology, 11, 976. doi:10.3389/fimmu.2020.00976. https://pubmed.ncbi.nlm.nih.gov/32547545/

3. Rubinstein, Artem, Kudryavtsev, Igor, Arsentieva, Natalia, Isakov, Dmitry, Totolian, Areg A. . CXCR3-Expressing T Cells in Infections and Autoimmunity. In Frontiers in bioscience (Landmark edition), 29, 301. doi:10.31083/j.fbl2908301. https://pubmed.ncbi.nlm.nih.gov/39206903/

4. Yuan, Zhuo. 2023. Research progress of CXCR3 inhibitors. In Anti-cancer drugs, 35, 36-45. doi:10.1097/CAD.0000000000001543. https://pubmed.ncbi.nlm.nih.gov/37694856/