CCL27–CCR10 interactions regulate T cell–mediated skin inflammation

Abstract

The skin-associated chemokine CCL27 (also called CTACK, ALP and ESkine) and its receptor CCR10 (GPR-2) mediate chemotactic responses of skin-homing T cells in vitro. Here we report that most skin-infiltrating lymphocytes in patients suffering from psoriasis, atopic or allergic-contact dermatitis express CCR10. Epidermal basal keratinocytes produced CCL27 protein that bound to extracellular matrix, mediated adhesion and was displayed on the surface of dermal endothelial cells. Tumor necrosis factor-alpha and interleukin-1beta induced CCL27 production whereas the glucocorticosteroid clobetasol propionate suppressed it. Circulating skin-homing CLA+ T cells, dermal microvascular endothelial cells and fibroblasts expressed CCR10 on their cell surface. In vivo, intracutaneous CCL27 injection attracted lymphocytes and, conversely, neutralization of CCL27-CCR10 interactions impaired lymphocyte recruitment to the skin leading to the suppression of allergen-induced skin inflammation. Together, these findings indicate that CCL27-CCR10 interactions have a pivotal role in T cell-mediated skin inflammation.

CXCR3 is required for migration to dermal inflammation by normal andin vivo activated T cells: differential requirements by CD4 and CD8 memory subsets

“…Previous studies have shown that CXCR3 is expressed, together with several other CKR, on T cells in inflamed tissues [1][2][3][4][5][6], and in dermal inflammation the T cell expression of the skin-homing CKR CCR4 and CCR10 has been the subject of focus [12][13][14][15][16]. In addition, CCR2, CCR5 and CXCR6 are also present on infiltrated T cells [4,5].…”

“…However, CXCR3 and CCR5 are also expressed on T cells in the skin, and CXCR3 can be co-expressed with CCR4 and CCR5. Furthermore, T cell migration to dermal inflammation is normal in CCR4-deficient mice, but is inhibited by anti-CCL27 [14,16]. Thus, the role of CXCR3 relative to CCR4 and CCR10, as well as to other inflammatory T cell-associated CKR, such as CCR5, CCR2, CXCR6 etc., is unclear.…”

“…In contact sensitivity and in psoriasis, many of the infiltrating T lymphocytes in the skin express abundant CCR4 and CCR10 [12][13][14][15][16]. These CCR4 + cells also express the cutaneous lymphocyte antigen (CLA), a ligand for E-selectin [12,17,18].…”

Cutaneous T‐cell lymphoma: 2011 update on diagnosis, risk‐stratification, and management

“…The overwhelming majority of skin-resident T cells are CD45RO 1 memory T cells expressing the skin-homing addressin CLA, which binds E-selectin on post-capillary venules in the skin and is required for lymphocyte rolling [15]. Skin-resident T cells highly express the chemokine receptors CCR4, CCR6, and CCR10, among others, required for their migration into the skin [15][16][17]. In contrast to central memory T cells (T CM ) expressing CCR7 and L-selectin, required for lymph-node homing and circulation in the peripheral blood, effector memory T cells (T EM ) form a persistent population of tissue-resident cells capable of rapidly responding to antigenic rechallenge and comprise 80% of T cells residing in normal skin [15].…”

Induction of organ‐selective CD4+ regulatory T cell homing

“…Among these homing receptors (HR), the integrin a 4 b 7 [5,6] and the chemokine receptor CCR9 [7][8][9] mediate the homing of T cell subsets to GALT such as mesenteric LN (mLN) and Peyer's patches (PP) and to the small intestinal lamina propria and the mucosal epithelium. In contrast, T cell trafficking to the skin is mediated by P-(P-lig) and E-(E-lig) selectin ligands [10,11] as well as CCR4 and CCR10 [12][13][14].…”