ArticleProceedings of the National Academy of Sciences of the United States of America2012
Transcription factor IRF4 determines germinal center formation through follicular T-helper cell differentiation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers.
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118 citing papers in PubMed, 194 citations in OpenAlex.
- Epigenetic landscape, key transcriptional regulators, and in vivo identification of human Tr1 cells.Science advances · 2026Article
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- Aging restricts maturation of CXCL13bioRxiv : the preprint server for biology · 2026Article
- The MEK1/2-IRF4 axis fosters T follicular helper cell differentiationand antitumor humoral immune response.Journal of translational medicine · 2026Article
- Interferon regulatory factor 4 as a context-dependent regulator of inflammation: transcriptional and epigenetic control, skin diseases, and translational challenges.Frontiers in immunology · 2026Review
- An overview of host immune responses against Leishmania spp. infections.Human molecular genetics · 2025Review
- Naringenin as a phytogenic adjuvant systematically enhances the protective efficacy of H9N2 inactivated vaccine through coordinated innate-adaptive immune priming in chickens.Poultry science · 2025Article
- The transcription factor IRF4 regulates the homeostasis and function of intestinal ILC3s.iScience · 2025Article
- Follicular Helper T Cells: Potential Interventional Targets in Atherosclerosis.Journal of immunology research · 2025Review
- Differentiation and regulation of CD4Cellular and molecular life sciences : CMLS · 2024Review
- Suppression of SENP3 enhances macrophage alternative activation by mediating IRF4 de-SUMOylation in ESCC progression.Cell communication and signaling : CCS · 2024Article
- Transcriptional regulation of Tfh dynamics and the formation of immunological synapses.Experimental & molecular medicine · 2024Review
- Tlr9 deficiency in B cells leads to obesity by promoting inflammation and gut dysbiosis.Nature communications · 2024Article
- PRMT5 Promotes T follicular helper Cell Differentiation and Germinal Center Responses during Influenza Virus Infection.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Defective mitochondria remodelling in B cells leads to an aged immune response.Nature communications · 2024Article
- Integrated analysis of lncRNA and mRNA expression profiles in cutaneous leishmaniasis lesions caused byFrontiers in cellular and infection microbiology · 2024Article
- Interferon regulatory factor 4 plays a pivotal role in the development of aGVHD-associated colitis.Oncoimmunology · 2024Article
- CD4Nature immunology · 2024Article
- Intralesional gene expression profile of JAK-STAT signaling pathway and associated cytokines inFrontiers in immunology · 2024Article
- Article
58 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Follicular T-helper (T(FH)) cells cooperate with GL7(+)CD95(+) germinal center (GC) B cells to induce antibody maturation. Herein, we identify the transcription factor IRF4 as a T-cell intrinsic precondition for T(FH) cell differentiation and GC formation. After immunization with protein or infection with the protozoon Leishmania major, draining lymph nodes (LNs) of IFN-regulatory factor-4 (Irf4(-/-)) mice lacked GCs and GC B cells despite developing normal initial hyperplasia. GCs were also absent in Peyer's patches of naive Irf4(-/-) mice. Accordingly, CD4(+) T cells within the LNs and Peyer's patches failed to express the T(FH) key transcription factor B-cell lymphoma-6 and other T(FH)-related molecules. During chronic leishmaniasis, the draining Irf4(-/-) LNs disappeared because of massive cell death. Adoptive transfer of WT CD4(+) T cells or few L. major primed WT T(FH) cells reconstituted GC formation, GC B-cell differentiation, and LN cell survival. In support of a T-cell intrinsic IRF4 activity, Irf4(-/-) T(FH) cell differentiation was not rescued by close neighborhood to transferred WT T(FH) cells. Together with its known B lineage-specific roles during plasma cell maturation and class switch, our study places IRF4 in the center of antibody production toward T-cell-dependent antigens.
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