ArticleCellular & molecular immunology2023
Insm1 regulates mTEC development and immune tolerance.
Article in Cellular & molecular immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 11 citations in OpenAlex.
- Decoding Spatial Heterogeneity and Multi-Omics Regulation with Hierarchical Graph Learning.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Runx3 instructs AireJournal of autoimmunity · 2026Article
- Spatial cartography of human thymus enables the geopositioning of lineage transcription factors in rare mimetic thymic epithelial cells.Nature communications · 2026Article
- AIRE transcriptional condensates in central tolerance: a multiscale mechanistic perspective.Frontiers in immunology · 2026Review
- Regulatory interplay of cyclin D1 and INSM1 in suppressing INSL6 expression: Implications for breast cancer biology.Biochemistry and biophysics reports · 2025Article
- An iPSC-based in vitro model recapitulates human thymic epithelial development and multi-lineage specification.Nature communications · 2025Article
- Thymic Mimetic Cells: Evolutionarily Ancient Mirrors of the Periphery.Immunological reviews · 2025Review
- Structural insights into a highly flexible zinc finger module unravel INSM1 function in transcription regulation.Nature communications · 2025Article
- Thymic Mimetic Cells: Ontogeny as Immunology.Annual review of cell and developmental biology · 2024Review
- Insm1: orchestrating cellular mimicry in the thymus medulla.Cellular & molecular immunology · 2024Article
- Immune tolerance and the prevention of autoimmune diseases essentially depend on thymic tissue homeostasis.Frontiers in immunology · 2024Review
- Hnf4 activates mimetic-cell enhancers to recapitulate gut and liver development within the thymus.The Journal of experimental medicine · 2023Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
The expression of self-antigens in medullary thymic epithelial cells (mTECs) is essential for the establishment of immune tolerance, but the regulatory network that controls the generation and maintenance of the multitude of cell populations expressing self-antigens is poorly understood. Here, we show that Insm1, a zinc finger protein with known functions in neuroendocrine and neuronal cells, is broadly coexpressed with an autoimmune regulator (Aire) in mTECs. Insm1 expression is undetectable in most mimetic cell populations derived from mTECs but persists in neuroendocrine mimetic cells. Mutation of Insm1 in mice downregulated Aire expression, dysregulated the gene expression program of mTECs, and altered mTEC subpopulations and the expression of tissue-restricted antigens. Consistent with these findings, loss of Insm1 resulted in autoimmune responses in multiple peripheral tissues. We found that Insm1 regulates gene expression in mTECs by binding to chromatin. Interestingly, the majority of the Insm1 binding sites are co-occupied by Aire and enriched in superenhancer regions. Together, our data demonstrate the important role of Insm1 in the regulation of the repertoire of self-antigens needed to establish immune tolerance.
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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.