ArticleGenes & development2015
The E-Id protein axis modulates the activities of the PI3K-AKT-mTORC1-Hif1a and c-myc/p19Arf pathways to suppress innate variant TFH cell development, thymocyte expansion, and lymphomagenesis.
Article in Genes & development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 38 citations in OpenAlex.
- HEB Restrains Effector Gene Expression during Early CD8Molecular and cellular biology · 2025Article
- Shifting gears: Id3 enables recruitment of E proteins to new targets during T cell development and differentiation.Frontiers in immunology · 2022Review
- Helix-Loop-Helix Proteins in Adaptive Immune Development.Frontiers in immunology · 2022Review
- MonoallelicFrontiers in immunology · 2022Article
- The E-Id Axis Instructs Adaptive Versus Innate Lineage Cell Fate Choice and Instructs Regulatory T Cell Differentiation.Frontiers in immunology · 2022Review
- Providing a Helping Hand: Metabolic Regulation of T Follicular Helper Cells and Their Association With Disease.Frontiers in immunology · 2022Review
- Bursty gene expression and mRNA decay pathways orchestrate B cell activation.Science advances · 2021Article
- Ontogenic timing, T cell receptor signal strength, and Notch signaling direct γδ T cell functional differentiation in vivo.Cell reports · 2021Article
- The Evolution of Rag Gene Enhancers and Transcription Factor E and Id Proteins in the Adaptive Immune System.International journal of molecular sciences · 2021Review
- Functional differentiation and regulation of follicular T helper cells in inflammation and autoimmunity.Immunology · 2021Review
- Inhibitor of Differentiation-2 Protein Ameliorates DSS-Induced Ulcerative Colitis by Inhibiting NF-κB Activation in Neutrophils.Frontiers in immunology · 2021Article
- The Interplay Between Chromatin Architecture and Lineage-Specific Transcription Factors and the Regulation ofFrontiers in immunology · 2021Review
- Article
- A Thpok-Directed Transcriptional Circuitry Promotes Bcl6 and Maf Expression to Orchestrate T Follicular Helper Differentiation.Immunity · 2019Article
- Programming for T-lymphocyte fates: modularity and mechanisms.Genes & development · 2019Review
- Helix-loop-helix proteins and the advent of cellular diversity: 30 years of discovery.Genes & development · 2019Review
- The UPR Activator ATF6 Responds to Proteotoxic and Lipotoxic Stress by Distinct Mechanisms.Developmental cell · 2018Article
- Paradoxical role of Id proteins in regulating tumorigenic potential of lymphoid cells.Frontiers of medicine · 2018Review
- Cancer metabolism: New insights into classic characteristics.The Japanese dental science review · 2018Review
- Three-step transcriptional priming that drives the commitment of multipotent progenitors toward B cells.Genes & development · 2018Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
It is now well established that the E and Id protein axis regulates multiple steps in lymphocyte development. However, it remains unknown how E and Id proteins mechanistically enforce and maintain the naïve T-cell fate. Here we show that Id2 and Id3 suppressed the development and expansion of innate variant follicular helper T (TFH) cells. Innate variant TFH cells required major histocompatibility complex (MHC) class I-like signaling and were associated with germinal center B cells. We found that Id2 and Id3 induced Foxo1 and Foxp1 expression to antagonize the activation of a TFH transcription signature. We show that Id2 and Id3 acted upstream of the Hif1a/Foxo/AKT/mTORC1 pathway as well as the c-myc/p19Arf module to control cellular expansion. We found that mice depleted for Id2 and Id3 expression developed colitis and αβ T-cell lymphomas. Lymphomas depleted for Id2 and Id3 expression displayed elevated levels of c-myc, whereas p19Arf abundance declined. Transcription signatures of Id2- and Id3-depleted lymphomas revealed similarities to genetic deficiencies associated with Burkitt lymphoma. We propose that, in response to antigen receptor and/or cytokine signaling, the E-Id protein axis modulates the activities of the PI3K-AKT-mTORC1-Hif1a and c-myc/p19Arf pathways to control cellular expansion and homeostatic proliferation.
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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.