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

Ming Feng Chiang, Shii Yi Yang, I. Ying Lin, Jin Bon Hong, Sung Jan Lin, Hsia Yuan Ying, Chun Ming Chen, Shih Ying Wu, Fu-Tong Liu, Kuo I. Lin

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

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

Original languageEnglish (US)
Pages (from-to)6476-6481
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number16
DOIs
StatePublished - Apr 16 2013
Externally publishedYes

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