Abstract
IL-22 is a potent pro-inflammatory cytokine upregulated in psoriasis and in other inflammatory diseases. The function of IL-22 is regulated by the soluble scavenging receptor, IL-22 binding protein (IL-22BP or IL-22RA2). However, the role and regulation of IL-22BP itself in the pathogenesis of inflammatory disease remain unclear. We used the TLR7 agonist Imiquimod (IMQ) to induce a psoriasis-like skin disease in mice and found a strong downregulation of IL-22BP in the affected skin as well as in the lymph nodes of animals treated with IMQ. We also analysed psoriatic skin of patients and compared this to skin of healthy donors. Interestingly, IL-22BP expression was similarly downregulated in skin biopsies of psoriasis patients compared to the skin of healthy donors. Since IL-22BP is expressed foremost in dendritic cells, we characterized its expression in monocyte-derived dendritic cells (MoDC) during maturation. In this way, we found Prostaglandin E2 (PGE2) to be a potent suppressor of IL-22BP expression in vitro. We conclude that regulation of IL-22BP by inflammatory mediators is an important step for the progression of inflammation in the skin and possibly also in other autoimmune diseases.
Highlights
IL-22 is a potent pro-inflammatory cytokine upregulated in psoriasis and in other inflammatory diseases
IL-22BP expression is downregulated in the skin and in the skin-draining lymph nodes of IMQ-induced psoriasis mice
We found substantial IL-22BP mRNA expression in the dorsal skin as well as in the skin-draining lymph nodes of healthy mice (Fig. 1C)
Summary
IL-22 is a potent pro-inflammatory cytokine upregulated in psoriasis and in other inflammatory diseases. IL-22BP expression was downregulated in skin biopsies of psoriasis patients compared to the skin of healthy donors. We conclude that regulation of IL-22BP by inflammatory mediators is an important step for the progression of inflammation in the skin and possibly in other autoimmune diseases. The cytokine has been shown to play a crucial role in the pathogenesis of several autoimmune diseases[6]. It has been recently shown that IL-22BP expressed by T cells plays an important role for IBD development in humans and IBD mouse models[15]. IL-22BP expression by human eosinophils in the gut may paly a detrimental role by inhibiting the protective effects of IL-22 in intestinal inflammation[16]. Correspondence and requests for materials should be addressed to F.C.K
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