Cited by 167Psoriasis: Treatment and PathogenesisT-cell and B-cell ImmunologyCytokine Signaling Pathways and Interactions

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Interleukin-23-Induced Transcription Factor Blimp-1 Promotes Pathogenicity of T Helper 17 Cells

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Jain, Renu, Chen, Yi, Kanno, Yuka, Joyce-Shaikh, Barbara, Vahedi, Golnaz, Hirahara, Kiyoshi, Blumenschein, Wendy M., Sukumar, Selvakumar, Haines, Christopher J., Sadekova, Svetlana, McClanahan, Terrill K., McGeachy, Mandy J., O’Shea, John J., Cua, Daniel J.·2016·Immunity

DOI 10.1016/j.immuni.2015.11.009PMC PMC11608061

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Abstract

Interleukin-23 (IL-23) is a pro-inflammatory cytokine required for the pathogenicity of T helper 17 (Th17) cells but the molecular mechanisms governing this process remain unclear. We identified the transcription factor Blimp-1 (Prdm1) as a key IL-23-induced factor that drove the inflammatory function of Th17 cells. In contrast to thymic deletion of Blimp-1, which causes T cell development defects and spontaneous autoimmunity, peripheral deletion of this transcription factor resulted in reduced Th17 activation and reduced severity of autoimmune encephalomyelitis. Furthermore, genome-wide occupancy and overexpression studies in Th17 cells revealed that Blimp-1 co-localized with transcription factors RORγt, STAT-3, and p300 at the Il23r, Il17a/f, and Csf2 cytokine loci to enhance their expression. Blimp-1 also directly bound to and repressed cytokine loci Il2 and Bcl6. Taken together, our results demonstrate that Blimp-1 is an essential transcription factor downstream of IL-23 that acts in concert with RORγt to activate the Th17 inflammatory program.

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Authors: Jain, R., Chen, Y., Kanno, Y., Joyce-Shaikh, B., Vahedi, G., Hirahara, K., Blumenschein, W. M., Sukumar, S., Haines, C. J., Sadekova, S., McClanahan, T. K., McGeachy, M. J., O’Shea, J. J., & Cua, D. J.
Affiliations: Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
National Institutes of Health (US)
Corresponding author: Cua, Daniel J.
ORCID: Jain, Renu
Chen, Yi
Kanno, Yuka
Vahedi, Golnaz
Hirahara, Kiyoshi
Blumenschein, Wendy M.
Sukumar, Selvakumar
Sadekova, Svetlana
McGeachy, Mandy J.
O’Shea, John J.
Venue: Immunity
Publisher: Elsevier BV
Published: 2016-01
Volume: 44
Issue: 1
Pages: 131-142
ISSN: 1074-7613 (ISSN-L)
DOI: 10.1016/j.immuni.2015.11.009
PMC: PMC11608061
OpenAlex: W2196731768
Cited by: 167
References: 36
Citations by year: 2026: 10 · 2025: 9 · 2024: 14 · 2023: 16 · 2022: 19 · 2021: 20 · 2020: 18 · 2019: 11 · 2018: 12 · 2017: 24 · 2016: 13
FWCI: 8.05
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 384 d)
Locations: Immunity (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Institute of Arthritis and Musculoskeletal and Skin Diseases (ZIAAR041159)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Keywords: IL-23, Blimp-1, Th17 cells, RORγt, STAT3, P300, transcriptional repression, autoimmune encephalomyelitis, cytokine gene expression, BCL6, Th17 cell differentiation
MeSH terms: Positive Regulatory Domain I-Binding Factor 1, Animals, Cell Differentiation, Cell Separation, Encephalomyelitis, Autoimmune, Experimental, Gene Expression Regulation, Inflammation, Lymphocyte Activation, Mice, Inbred C57BL, Mice, Transgenic, Transcription Factors, Transduction, Genetic, Mice, Knockout, Chromatin Immunoprecipitation, Mice, Interleukin-23, Th17 Cells, Real-Time Polymerase Chain Reaction

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Interleukin-23-Induced Transcription Factor Blimp-1 Promotes Pathogenicity of T Helper 17 Cells

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