Chemokine receptors in the pathogenesis and therapy of psoriasis

The roles of CD4+ T cell subtypes in psoriasis. Th cell subsets and Treg cells are differentiated from naïve T cells. Under conditions of healthy immune homeostasis, the activation of Th cells is, in part, regulated by Treg cells. T cell-mediated immune response is held in fine balance. In psoriasis, this balance is disrupted; pro-inflammatory cytokines produced from Th1 and Th17 cells dominate the cytokine profile. Solid arrows denote stimulatory actions, dashed arrows denote inhibitory actions.

The roles of chemokines and their receptors in psoriasis. CCR2-expressing monocytes and macrophages (Mϕ) migrate into epidermis via basal keratinocyte (KC)-derived CCL2, the CCR2 ligand. Circulating CCR4 and CXCR3-expressing Th1 cells move into epidermis from dermis via interaction with KC-derived CCL17 and/or CCL22, the CCR4 ligands, and CXCL9, CXCL10 and/or CXCL11, the CXCR3 ligands. CCR5-expressing CD3+ T cells and Mϕ migrate into epidermis through interaction with CCL3 and KC-derived CCL5, both CCR5 ligands. CCR6 has only one known chemokine ligand, CCL20. The selectivity of CCL20 for CCR6 allows recruitment of circulating CCR6-expressing cells, including Th17 cells, γδ T cells that express Th17 cytokines, and LCs into inflamed epidermis. CCR10-expressing cutaneous lymphocyte antigen (CLA)+, CD4+, and CD8+ T cells migrate into epidermis via KC-derived CCL27, the CCR10 ligand. CXCL8 is a common ligand for both CXCR1 and CXCR2 and is a potent chemoattractant for neutrophils. Plasmatoid dendritic cells (pDCs), which also express CXCR3, also traffic to inflamed epidermis. EC, endothelial cell; KC, keratinocyte; LC, Langerhans cell; Mϕ, macrophage; pDC, plasmatoid dendritic cell.