CCR4 and CXCR3 play different roles in the migration of T cells to inflammation in skin, arthritic joints, and lymph nodes

• Published in: European journal of immunology 2014-06, Vol.44 (6), p.1633-1643
• Main Authors: Al‐Banna, Nadia A., Vaci, Maria, Slauenwhite, Drew, Johnston, Brent, Issekutz, Thomas B.
• Format: Article
• Language: English
• Subjects: Animals; Arthritis; Arthritis, Experimental - genetics; Arthritis, Experimental - immunology; Arthritis, Experimental - pathology; Cell Movement - immunology; Chemokine receptors; Dermatitis - genetics; Dermatitis - immunology; Dermatitis - pathology; Immune system; Joints - immunology; Joints - pathology; Lymph Nodes - immunology; Lymph Nodes - pathology; Lymphocytes; Medical research; Mice; Mice, Knockout; Migration; Organ Specificity - genetics; Organ Specificity - immunology; Receptors, CCR4 - genetics; Receptors, CCR4 - immunology; Receptors, CXCR3 - genetics; Receptors, CXCR3 - immunology; Skin; Skin - immunology; Skin - pathology; T cells; T-Lymphocytes - immunology; T-Lymphocytes - pathology
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201343995

CCR4 and CXCR3 are expressed on several T‐cell subsets in inflamed tissues, yet their role in tissue‐specific recruitment is unclear. We examined the contributions of CCR4 and CXCR3 to T‐cell recruitment into inflamed joints in collagen‐induced arthritis, antigen‐draining lymph nodes (LNs) and dermal inflammatory sites (poly I:C, LPS, concanavalin A, and delayed type hypersensitivity), using labeled activated T cells from CXCR3−/−, CCR4−/−, and WT mice. Both CXCR3 and CCR4 deficiency reduced the development of arthritis, but did not affect Th1‐cell recruitment to the inflamed joints. Accumulation in inflamed LNs was highly CXCR3 dependent. In contrast, CCR4‐deficient Th1 cells had an increased accumulation in these LNs. Migration to all four dermal inflammatory sites by activated Th1 and T cytotoxic cells and memory CD4+ T cells was partially CXCR3‐dependent, but Treg‐cell migration was independent of CXCR3. The subset of cells expressing CCR4 has skin‐migrating properties, but CCR4 itself is not required for the migration. Thus, migration into these inflamed tissues is CCR4‐independent, and partially dependent on CXCR3, except for Treg cells, which require neither receptor. CCR4 may therefore affect retention of T cells in different tissues rather than trafficking out of the blood.