CCR4 and CXCR3 play different roles in the migration of T cells to inflammation in skin, arthritic joints, and lymph nodes.
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.
Department of Microbiology and Immunology, Dalhousie University, Halifax, Canada.
Nadia A
NA
Al-Banna
Maria
M
Vaci
Drew
D
Slauenwhite
Brent
B
Johnston
Thomas B
TB
Issekutz
D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D002465:Cell Movement / Q000276:immunology*; D003872:Dermatitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007596:Joints / Q000276:immunology* / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D054398:Receptors, CCR4 / Q000235:genetics / Q000276:immunology*; D054367:Receptors, CXCR3 / Q000235:genetics / Q000276:immunology*; D012867:Skin / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
C515355:Ccr4 protein, mouse; C515188:Cxcr3 protein, mouse; D054398:Receptors, CCR4; D054367:Receptors, CXCR3
Arthritis; Chemokine receptors; Migration; Skin; T cells