CCR4

C-C chemokine receptor type 4 (CCR4, CD194) is a G protein-coupled receptor that recognizes CCL17 (TARC) and CCL22 (MDC), two chemokines highly expressed in thymus and inflamed peripheral tissues. CCR4 defines a functionally polarized T-helper population: it marks Th2 cells, circulating skin-homing memory T cells bearing cutaneous lymphocyte antigen, and regulatory T cells, the latter exploiting CCR4 to access CCL17/CCL22-rich skin tumors and thymic microenvironments. Upon ligand engagement, CCR4 couples to Gαi, eliciting chemotaxis, integrin activation through Rap1, and calcium flux. Physiologically, CCR4 guides T-cell homing to skin and drives Th2 positioning in helminth infection and allergic dermatitis. Pathologically, CCR4 is expressed by the malignant cells of adult T-cell leukemia/lymphoma and cutaneous T-cell lymphoma (mycosis fungoides/Sézary syndrome), which constitutively traffic to CCL17/CCL22-secreting skin lesions; this dependency led to mogamulizumab, a defucosylated anti-CCR4 antibody approved for these lymphomas, and CCR4 antagonists are under study for asthma and atopic disease.