Danger-associated molecular patterns (DAMPs) are released from the stressed cells and play crucial roles in the inflammatory and auto-immune responses. Previously, our lab has demonstrated that keratinocytes’ apoptosis and necroptosis, two forms of programmed cell death, triggers skin inflammation. However, the downstream mechanisms and factors involved in cell death-mediated inflammation and epithelial-immune cell communication are poorly understood.
Clec4e (Mincle) is a C-type lectin DAMP receptor that senses DAMPs released from dying or injured cells as well as microbial molecular patterns. Interestingly, the expression of Mincle is restricted to immune cells, such as myeloid cells, in the skin. We hypothesize that Mincle expression in the skin is a crucial regulator of skin inflammation. To test this, we used an imiquimod-induced mouse model of skin inflammation. The treatment of mouse skin with imiquimod leads to Psoriasis, an inflammatory skin disease, like phenotype.
We observed amelioration of the epidermal thickening and inflammatory responses, which are the characteristics of imiquimod-induced skin inflammation, in the imiquimod-treated Mincle knockout (KO) compared to that of wild-type mice. Moreover, the overall body weight and erythema in the Mincle KO mice were also less pronounced compared to the wild-type mice. To address the underlying mechanisms by which Mincle deficiency inhibits the inflammatory responses in the skin, we analyzed immune cell infiltration using high parameter, multi-colour flow cytometry in the imiquimod-treated and untreated wild-type and Mincle KO skin. Interestingly, we observed a differential accumulation of immune cells, in particular, CD45+CD11b+Ly6G+ neutrophils, in the imiquimod-treated Mincle KO compared to wild-type skin. These results suggest an important immunomodulatory role of Mincle in skin inflammation and immune homeostasis.