ArticleImmunity2015
ICOS coreceptor signaling inactivates the transcription factor FOXO1 to promote Tfh cell differentiation.
Article in Immunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 158 papers.
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Who cites it
158 citing papers in PubMed, 232 citations in OpenAlex.
- Regulation of follicular helper T cell subset differentiation in health and disease.Journal of molecular medicine (Berlin, Germany) · 2026Review
- FOXP1 Knockdown Reprograms Th9 CAR-T Cells to Overcome Antigen Escape.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- T cell lymphomas: cancers of aberrant immune synapse signalling.Nature reviews. Immunology · 2026Review
- Ets1 represses Blimp1 to promote germinal center T follicular helper cell differentiation during viral infection.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Dnmt3a-dependent de novo DNA methylation enforces lineage commitment and preserves functionality of memory Th1 and Tfh cells.Cell reports · 2026Article
- APDS in a 3-year-old boy presenting with EBV viremia and hodgkin lymphoma associated with a novel germline heterozygous variant in PIK3CD and with characteristic immune phenotype but no upregulation of the T cell mTOR pathway.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2026Article
- Dual regulation of CXCR6Journal for immunotherapy of cancer · 2026Article
- CD27 and ICOS as Targets of PD-1/PD-L1 Signaling to Regulate Resident Memory CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Inducible T-Cell Co-Stimulator (ICOS) and ICOS Ligand: Dealing With a Two-Faced Cancer Immunoregulatory System.Cancer medicine · 2026Review
- Divergent cytokine and transcriptional signatures control functional T follicular helper cell heterogeneity.Nature immunology · 2025Article
- Integrative Genomic and Transcriptomic Analysis Reveals Targetable Vulnerabilities in Angioimmunoblastic T-Cell Lymphoma.American journal of hematology · 2025Article
- The costimulatory molecule ICOS limits memory-like properties and function of exhausted PD-1Immunity · 2025Article
- RORγt eTACs mediate oral tolerance and Treg induction.The Journal of experimental medicine · 2025Article
- Mitochondrial DNA oxidation propagates autoimmunity by enabling plasmacytoid dendritic cells to induce TNature immunology · 2025Article
- KMT2D coordinates antiviral CD4Cell reports · 2025Article
- NKT cells-a generalist in disease treatment and a new key to unlock immunotherapy.Immunotherapy · 2025Review
- IGF1 Signaling Regulates Neuropeptide Expression in Hypothalamic Neurons Under Physiological and Pathological Conditions.Endocrinology · 2025Article
- Identification of circulating Tfh/Th subsets as a biomarker of developed hospital-acquired pneumonia.Frontiers in immunology · 2025Article
- Influencing immunity: role of extracellular vesicles in tumor immune checkpoint dynamics.Experimental & molecular medicine · 2024Review
- In vivo CAR T cell therapy against angioimmunoblastic T cell lymphoma.Journal of experimental & clinical cancer research : CR · 2024Article
98 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
T follicular helper (Tfh) cells are essential in the induction of high-affinity, class-switched antibodies. The differentiation of Tfh cells is a multi-step process that depends upon the co-receptor ICOS and the activation of phosphoinositide-3 kinase leading to the expression of key Tfh cell genes. We report that ICOS signaling inactivates the transcription factor FOXO1, and a Foxo1 genetic deletion allowed for generation of Tfh cells with reduced dependence on ICOS ligand. Conversely, enforced nuclear localization of FOXO1 inhibited Tfh cell development even though ICOS was overexpressed. FOXO1 regulated Tfh cell differentiation through a broad program of gene expression exemplified by its negative regulation of Bcl6. Final differentiation to germinal center Tfh cells (GC-Tfh) was instead FOXO1 dependent as the Foxo1(-/-) GC-Tfh cell population was substantially reduced. We propose that ICOS signaling transiently inactivates FOXO1 to initiate a Tfh cell contingency that is completed in a FOXO1-dependent manner.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.