The crucial role of IL‐22 and its receptor in thymus and activation regulated chemokine production and T‐cell migration by house dust mite extract

Abstract

House dust mite (HDM) is known as one of the factors that causes atopic dermatitis (AD). Interleukin (IL)-22 and thymus and activation regulated chemokine (TARC) are related to skin inflammatory disease and highly expressed in AD lesions. However, the effects of HDM on IL-22 production in T cells and on TARC production and IL-22Rα receptor expression in keratinocytes are unknown. To identify the role of HDM in keratinocytes and T cells, we investigated IL-22Rα expression and TARC production in the human keratinocyte cell line HaCaT and IL-22 production in T cells treated with HDM extract as well as their roles in HDM-induced skin inflammation. HDM extract not only increased IL-22Rα expression and TARC production in HaCaT but also enhanced IL-22, tumor necrosis factor (TNF)-α and interferon (IFN)-γ production in T cells. The HDM extract-induced IL-22 from T cells significantly increased the production of IL-1α, IL-6 and TARC in HaCaT cells. In addition, we found that TARC produced in HDM extract-treated HaCaT induced T-cell recruitment. These results suggest that there is a direct involvement of HDM extract-induced IL-22 in TARC production and T-cell migration. Taken together, TARC production in HaCaT through the interaction between IL-22 and IL-22Rα facilitates T-cell migration. These data show one of the reasons for inflammation in the skin lesions of AD patients.

Thymus and activation‐regulated chemokine (TARC) in patients with psoriasis: Increased serum TARC levels in patients with generalized pustular psoriasis

“…Intriguingly, the serum TARC level positively correlated with the serum IL‐22 level in GPP patients. Jang et al 25 . has reported that house dust mite extract‐induced IL‐22 from T cells significantly increased TARC production in the human keratinocyte cell line, HaCaT.…”

Molecular Mechanisms of Cutaneous Inflammatory Disorder: Atopic Dermatitis

“…IL-22 and IL-17 synergistically increase the levels of S100 proteins and AMPs in the epidermis [12,136]. IL-22 secretion can be induced immediately in response to staphylococcal exotoxins and house dust mites and can potentially amplify chronic skin inflammation in patients with AD [137,138]. IL-22 can also stimulate CCL17 production from human keratinocytes and promote the migration of T cells into the skin [138].…”

“…IL-22 secretion can be induced immediately in response to staphylococcal exotoxins and house dust mites and can potentially amplify chronic skin inflammation in patients with AD [137,138]. IL-22 can also stimulate CCL17 production from human keratinocytes and promote the migration of T cells into the skin [138]. Upregulated IL-22 in chronic AD induces matrix metalloproteinase-3, a marker of remodeling; stromelysin-1; platelet-derived growth factor A; and CXCL5 (chemokine, CXC motif, ligand 5) [139].…”

Pseudolaric acid B attenuates atopic dermatitis-like skin lesions by inhibiting interleukin-17-induced inflammation

“…Recently, Th17 and Th22 cells have been implicated in AD-related immune dysregulation by amplifying the inflammatory response 11 . IL-17 and IL-22 are main effective cytokines of Th17 and Th22 cells, which could induce the secretion of IL-1β, TNF-α and other pro-inflammatory cytokines 12 , 13 . The functional IL-22 receptor consists of two receptor subunits, IL-22R1 and IL-10R2, among which IL-22R1 plays a much more important role than IL-10R2 during AD 13 .…”