CXCR3 is a G-protein coupled chemokine receptor that mediates immune cell recruitment and T cell-dependent inflammation through binding ELR-negative CXC chemokines (CXCL9, CXCL10, CXCL11) 1. CXCR3 is highly expressed on innate and adaptive lymphocytes, including Th1, Th17, CD8+ T cells, and regulatory T cells, driving calcium signaling and chemotaxis toward inflamed tissues 2. Mechanistically, CXCR3 expression is induced by interferon-gamma, creating a positive feedback loop that amplifies Th1-mediated immune responses 3. CXCR3 has emerged as critical in multiple diseases: in neuroinflammatory conditions (multiple sclerosis, encephalitis), vitiligo (where CXCR3+ CD8+ T cells execute melanocyte destruction), and cancer (where CXCR3+ Treg cell-dendritic cell interactions suppress anti-tumor immunity) 453. The receptor exists as multiple isoforms with opposing functions—CXCR3-A promotes tumor proliferation and metastasis while CXCR3-B induces growth suppression 1. CXCR3 also regulates memory B cell differentiation dependent on Tfh cell-derived interferon-gamma 6. Due to its central role in pathological inflammation, CXCR3 represents a therapeutic target, though few antagonists have entered clinical development 7.