Inducible deletion of the Blimp-1 gene in adult epidermis causes granulocyte-dominated chronic skin inflammation in mice

摘要: B lymphocyte-induced maturation protein-1 (Blimp-1) is a transcriptional repressor important for the differentiation and function of several types immune cells. Because skin serves as physical barrier acts an sentinel, we investigated whether Blimp-1 involved in epidermal function. We show that expression reduced lesions some human eczema samples stimulated primary keratinocytes. Epidermal-specific deletion PR domain containing 1, with ZNF (Prdm1), gene encoding Blimp-1, adult mice caused spontaneously inflamed characterized by massive dermal infiltration neutrophils/macrophages development chronic inflammation associated higher levels cytokines/chemokines, including granulocyte colony-stimulating factor (G-CSF), enhanced myelopoiesis bone marrow. Deletion Prdm1 epidermis also led to stronger inflammatory reactions tape-stripping test disease model contact dermatitis. The elevated G-CSF produced keratinocytes after vitro was mediated activation FBJ osteosarcoma oncogene (Fos) fos-like antigen 1 (Fosl1). Systemic increases contributed responses, because [colony stimulating 3, (Csf3)] prevented neutrophilia partially ameliorated Prdm1-deficient mice. Our findings indicate previously unreported restraining steady-state immunity.