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

Proc Natl Acad Sci U S A. 2013 Apr 16;110(16):6476-81. doi: 10.1073/pnas.1219462110. Epub 2013 Apr 1.


B lymphocyte-induced maturation protein-1 (Blimp-1) is a transcriptional 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 neutrophils/macrophages and development of chronic inflammation associated with higher levels of cytokines/chemokines, including granulocyte colony-stimulating factor (G-CSF), and enhanced myelopoiesis 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 osteosarcoma 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 unreported function for Blimp-1 in restraining steady-state epidermal barrier immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Dermatitis / genetics*
  • Dermatitis / physiopathology
  • Dinitrofluorobenzene
  • Epidermis / metabolism*
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Gene Deletion*
  • Granulocyte Colony-Stimulating Factor / metabolism
  • Immunoblotting
  • Keratinocytes / metabolism
  • Macrophages / immunology
  • Mice
  • Neutrophil Infiltration / immunology
  • Positive Regulatory Domain I-Binding Factor 1
  • Real-Time Polymerase Chain Reaction
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism


  • Cytokines
  • Prdm1 protein, mouse
  • Transcription Factors
  • Granulocyte Colony-Stimulating Factor
  • Dinitrofluorobenzene
  • Positive Regulatory Domain I-Binding Factor 1

Associated data

  • GEO/GSE34586