title: Inducible deletion of the Blimp-1 gene in adult epidermis causes granulocyte-dominated chronic skin inflammation in mice.
abstract: 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.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Ming-Feng
authors.initials: MF
authors.lastname: Chiang
authors.forename: Shii-Yi
authors.initials: SY
authors.lastname: Yang
authors.forename: I-Ying
authors.initials: IY
authors.lastname: Lin
authors.forename: Jin-Bon
authors.initials: JB
authors.lastname: Hong
authors.forename: Sung-Jan
authors.initials: SJ
authors.lastname: Lin
authors.forename: Hsia-Yuan
authors.initials: HY
authors.lastname: Ying
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Chen
authors.forename: Shih-Ying
authors.initials: SY
authors.lastname: Wu
authors.forename: Fu-Tong
authors.initials: FT
authors.lastname: Liu
authors.forename: Kuo-I
authors.initials: KI
authors.lastname: Lin
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D003872:Dermatitis / Q000235:genetics* / Q000503:physiopathology; D004139:Dinitrofluorobenzene; D004817:Epidermis / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D017353:Gene Deletion; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D015151:Immunoblotting; D015603:Keratinocytes / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D051379:Mice; D020556:Neutrophil Infiltration / Q000276:immunology; D000074462:Positive Regulatory Domain I-Binding Factor 1; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D016207:Cytokines; C513258:Prdm1 protein, mouse; D014157:Transcription Factors; D016179:Granulocyte Colony-Stimulating Factor; D004139:Dinitrofluorobenzene; D000074462:Positive Regulatory Domain I-Binding Factor 1