CCR6 is required for epidermal trafficking of γδ-T cells in an IL-23-Induced model of psoriasiform dermatitis

Tomotaka Mabuchi, Tej Pratap Singh, Tomonori Takekoshi, Guang Fu Jia, Xuesong Wu, Mandy C. Kao, Ido Weiss, Joshua M. Farber, Samuel T Hwang

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)164-171
Number of pages8
JournalJournal of Investigative Dermatology
Volume133
Issue number1
DOIs
StatePublished - Jan 2013
Externally publishedYes

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Dermatitis
Interleukin-23
T-cells
T-Lymphocytes
Knockout Mice
CCR6 Receptors
Epidermis
Skin
Dermis
T-Lymphocyte Subsets
Psoriasis
Ear
Cytokines

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

CCR6 is required for epidermal trafficking of γδ-T cells in an IL-23-Induced model of psoriasiform dermatitis. / Mabuchi, Tomotaka; Singh, Tej Pratap; Takekoshi, Tomonori; Jia, Guang Fu; Wu, Xuesong; Kao, Mandy C.; Weiss, Ido; Farber, Joshua M.; Hwang, Samuel T.

In: Journal of Investigative Dermatology, Vol. 133, No. 1, 01.2013, p. 164-171.

Research output: Contribution to journalArticle

Mabuchi, Tomotaka ; Singh, Tej Pratap ; Takekoshi, Tomonori ; Jia, Guang Fu ; Wu, Xuesong ; Kao, Mandy C. ; Weiss, Ido ; Farber, Joshua M. ; Hwang, Samuel T. / CCR6 is required for epidermal trafficking of γδ-T cells in an IL-23-Induced model of psoriasiform dermatitis. In: Journal of Investigative Dermatology. 2013 ; Vol. 133, No. 1. pp. 164-171.
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abstract = "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.",
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