MCPIP1 is an RNase essential for the degradation of transcripts encoding inflammatory proteins. Recent studies indicated that MCPIP1 may regulate pathological processes in the skin. It was shown that MCPIP1 expression is upregulated in psoriatic epidermis and restricts IL-17A and IL-17C-dependent skin inflammation. However, the exact role of MCPIP1 in epidermis is still poorly understood. To examine whether MCPIP1 is important for the epidermal barrier, homeostasis and skin inflammation, we generated keratinocyte-specific MCPIP1 deficient mice (MCPIP1EKO) by means of K14-Cre mediated gene deletion. Using RNA-seq and qPCR we determined potential target genes of MCPIP1 in keratinocytes isolated from MCPIP1EKO mice. Inhibition of MCPIP1 resulted in the upregulation of mRNAs encoding cornified envelope proteins, cytokines, chemokines and antimicrobial peptides. Newborn MCPIP1EKO mice have reduced body weight but do not develop any visible abnormality in the epidermis. However, after inducing skin inflammation by topical treatment with IMQ, MCPIP1EKO mice developed psoriasis-like skin symptoms more progressively, macroscopi- cally apparent as increasing redness and scaling as compared to control mice. Microscopy studies revealed psoriasis-specific pathology characterized by acanthosis, elongated rete-like ridges, parakeratosis and infiltration of immune cells. Moreover, mRNA analysis of skin samples by qPCR revealed strong upregulation of psoriasis-associated genes in MCPIP1EKO mice. Altogether, our data indicate that MCPIP1 in keratinocytes is an important regulator of skin homeostasis and also plays a significant role in the pathogenesis of psoriasis.

Keratinocyte-specific ablation of MCPIP1 is sufficient to aggravate skin inflammation