ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Id3 and Id2 act as a dual safety mechanism in regulating the development and population size of innate-like γδ T cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- Article
- TCRγ constant usage tunes human γδ T cell antigen sensitivity, thymic programming, and peripheral function.Science immunology · 2026Article
- Developmental hematopoiesis: innate programming of αβ T cells.Experimental hematology · 2026Review
- HEB collaborates with TCR signaling to upregulatebioRxiv : the preprint server for biology · 2025Article
- E proteins control the development of NKγδT cells through their invariant T cell receptor.Nature communications · 2024Article
- Article
- Article
- Signaling networks controlling ID and E protein activity in T cell differentiation and function.Frontiers in immunology · 2022Review
- Helix-Loop-Helix Proteins in Adaptive Immune Development.Frontiers in immunology · 2022Review
- Single-cell RNA-Seq reveals a highly coordinated transcriptional program in mouse germ cells during primordial follicle formation.Aging cell · 2021Article
- The E protein-TCF1 axis controls γδ T cell development and effector fate.Cell reports · 2021Article
- Reference Transcriptomes of Porcine Peripheral Immune Cells Created Through Bulk and Single-Cell RNA Sequencing.Frontiers in genetics · 2021Article
- Development of Type 2 Innate Lymphoid Cells Is Selectively Inhibited by Sustained E Protein Activity.ImmunoHorizons · 2019Article
- The Concerted Action of E2-2 and HEB Is Critical for Early Lymphoid Specification.Frontiers in immunology · 2019Article
- Id3 Restricts γδ NKT Cell Expansion by Controlling Egr2 and c-Myc Activity.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Id Proteins Suppress E2A-Driven Invariant Natural Killer T Cell Development prior to TCR Selection.Frontiers in immunology · 2018Article
- Three distinct developmental pathways for adaptive and two IFN-γ-producing γδ T subsets in adult thymus.Nature communications · 2017Article
- Id2 Collaborates with Id3 To Suppress Invariant NKT and Innate-like Tumors.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Zbtb16 (PLZF) is stably suppressed and not inducible in non-innate T cells via T cell receptor-mediated signaling.Scientific reports · 2015Article
- Transcription factor networks directing the development, function, and evolution of innate lymphoid effectors.Annual review of immunology · 2015Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The innate-like T cells expressing Vγ1.1 and Vδ6.3 represent a unique T cell lineage sharing features with both the γδ T and the invariant NKT cells. The population size of Vγ1.1(+)Vδ6.3(+) T cells is tightly controlled and usually contributes to a very small proportion of thymic output, but the underlying mechanism remains enigmatic. Deletion of Id3, an inhibitor of E protein transcription factors, can induce an expansion of the Vγ1.1(+)Vδ6.3(+) T cell population. This phenotype is much stronger on the C57BL/6 background than on the 129/sv background. Using quantitative trait linkage analysis, we identified Id2, a homolog of Id3, to be the major modifier of Id3 in limiting Vγ1.1(+)Vδ6.3(+) T cell expansion. The Vγ1.1(+)Vδ6.3(+) phenotype is attributed to an intrinsic weakness of Id2 transcription from Id2 C57BL/6 allele, leading to an overall reduced dosage of Id proteins. However, complete removal of both Id2 and Id3 genes in developing T cells suppressed the expansion of Vγ1.1(+)Vδ6.3(+) T cells because of decreased proliferation and increased cell death. We showed that conditional knockout of Id2 alone is sufficient to promote a moderate expansion of γδ T cells. These regulatory effects of Id2 and Id3 on Vγ1.1(+)Vδ6.3(+) T cells are mediated by titration of E protein activity, because removing one or more copies of E protein genes can restore Vγ1.1(+)Vδ6.3(+) T cell expansion in Id2 and Id3 double conditional knockout mice. Our data indicated that Id2 and Id3 collaboratively control survival and expansion of the γδ lineage through modulating a proper threshold of E proteins.
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