CCR6 is required for epidermal trafficking of γδ-T cells in an IL-23-induced model of psoriasiform dermatitis.
A subset of CC chemokine receptor-6(+) (CCR6(+)), γδ-low (GDL) T cells that express Th17 cytokines in mouse skin participates in IL-23-induced psoriasiform dermatitis. We use CCR6-deficient (knockout, KO) and wild-type (WT) mice to analyze skin trafficking patterns of GDL T cells and function-blocking mAbs to determine the role of CCR6 in IL-23-mediated dermatitis. Herein, CCL20 was highly upregulated in IL-23-injected WT mouse ear skin as early as 24 hours after initial treatment, and large numbers of CCR6(+) cells were observed in the epidermis of IL-23-injected WT mice. Anti-CCL20 mAbs reduced psoriasiform dermatitis and blocked recruitment of GDL T cells to the epidermis. In CCR6 KO mice, GDL T cells failed to accumulate in the epidermis after IL-23 treatment, but the total numbers of GDL T cells in the dermis of WT and CCR6 KO mice were equivalent. There was an ∼70% reduction in the proportion of IL-22(+) GDL T cells in the dermis of CCR6 KO mice (vs WT mice), suggesting that effector function and epidermal recruitment of GDL T cells are impaired in CCR6-deficient mice. Thus, these data show that CCR6 regulates epidermal trafficking of γδ-T-cell subsets in the skin and suggest the potential of CCR6 as a therapeutic target for psoriasis.
Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wi, USA.
Tomotaka
T
Mabuchi
Tej Pratap
TP
Singh
Tomonori
T
Takekoshi
Guang-Fu
GF
Jia
Xuesong
X
Wu
Mandy C
MC
Kao
Ido
I
Weiss
Joshua M
JM
Farber
Sam T
ST
Hwang
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D054418:Chemokine CCL20 / Q000276:immunology; D003872:Dermatitis / Q000276:immunology* / Q000473:pathology; D004817:Epidermis / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D053759:Interleukin-23 / Q000009:adverse effects*; D007378:Interleukins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011565:Psoriasis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000187:drug effects / Q000276:immunology; D054399:Receptors, CCR6 / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D000097043:Interleukin-22
D019138:Antibodies, Blocking; D054418:Chemokine CCL20; D053759:Interleukin-23; D007378:Interleukins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D054399:Receptors, CCR6; D000097043:Interleukin-22; C493447:CCL20 protein, mouse; C498126:CCR6 protein, mouse