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Cited by 42Dermatology and Skin DiseasesPsoriasis: Treatment and PathogenesisContact Dermatitis and Allergies

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

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Chiang, Ming-Feng, Yang, Shii-Yi, Lin, I-Ying, Hong, Jin-Bon, Lin, Sung-Jan, Ying, Hsia-Yuan, Chen, Chun-Ming, Wu, Shih-Ying +2 more·2013·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1219462110PMC PMC3631680
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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.

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  • Blimp1 functions in terminally differentiated sebocytes as well as in granular IFE cells.

    “Alternatively, it has recently been suggested that Blimp1 functions in terminally differentiated sebocytes8 as well as in granular IFE cells9, 10.”

    From Blimp1+ cells generate functional mouse sebaceous gland organoids in vitro (2019) · cites this paper as [9]

  • Terminally differentiated sebocytes and granular layer IFE keratinocytes are marked by the Blimp1 protein.

    “Subsequently, it was described that terminally differentiated sebocytes8, as well as granular layer IFE keratinocytes9, 10 are marked by the Blimp1 protein.”

    From Blimp1+ cells generate functional mouse sebaceous gland organoids in vitro (2019) · cites this paper as [9]

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Cited by

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Authors
Chiang, M.-F., Yang, S.-Y., Lin, I.-Y., Hong, J.-B., Lin, S.-J., Ying, H.-Y., Chen, C.-M., Wu, S.-Y., Liu, F.-T., & Lin, K.-I.
Affiliations
  • Genomics Research Center, Academia Sinica (TW)
  • National Taiwan University (TW)
  • National Yang Ming University (TW)
  • Institute of Information Science, Academia Sinica (TW)
  • Institute of Biomedical Sciences, Academia Sinica (TW)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2013-04
Volume
110
Issue
16
Pages
6476-6481
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1219462110
PMC
PMC3631680
OpenAlex
W2077337651
Cited by
42
References
1
Citations by year
2026: 1 · 2025: 4 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 5 · 2016: 6 · 2015: 3 · 2014: 8 · 2013: 2
FWCI
7.40
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Science Council (100-2628-B-001-015-MY4)
  • Academia Sinica
Topics
  • Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
  • Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
  • Health Sciences › Medicine › Dermatology › Contact Dermatitis and Allergies
Keywords
Blimp-1, epidermis, chronic skin inflammation, granulocyte colony-stimulating factor, keratinocytes, neutrophil infiltration, myelopoiesis, FOS, FOSL1, contact dermatitis, atopic dermatitis, transcriptional repressor, gene deletion
MeSH terms
Positive Regulatory Domain I-Binding Factor 1, Animals, Dermatitis, Dinitrofluorobenzene, Epidermis, Flow Cytometry, Fluorescent Antibody Technique, Macrophages, Transcription Factors, Immunoblotting, Keratinocytes, Granulocyte Colony-Stimulating Factor, Cytokines, Gene Deletion, Neutrophil Infiltration, Mice, Real-Time Polymerase Chain Reaction

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