ArticleFrontiers in immunology2021
An IRF1-IRF4 Toggle-Switch Controls Tolerogenic and Immunogenic Transcriptional Programming in Human Langerhans Cells.
Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed, 15 citations in OpenAlex.
- Single-Cell Transcriptome Analysis Reveals IRF1-Driven Epithelial States and Glycosaminoglycan-Glycolysis Coupling in Cisplatin-Resistant HGSOC.Cancer informatics · 2026Article
- Human epidermal Langerhans cells induce tolerance and hamper T cell function upon tick-borne pathogen transmission.Nature communications · 2025Article
- A logic-incorporated gene regulatory network deciphers principles in cell fate decisions.eLife · 2024Article
- Impaired expression of metallothioneins contributes to allergen-induced inflammation in patients with atopic dermatitis.Nature communications · 2023Article
- Localized immune surveillance of primary melanoma in the skin deciphered through executable modeling.Science advances · 2023Article
- Review
- Transcriptional programming of immunoregulatory responses in human Langerhans cells.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Langerhans cells (LCs) reside in the epidermis as a dense network of immune system sentinels, coordinating both immunogenic and tolerogenic immune responses. To determine molecular switches directing induction of LC immune activation, we performed mathematical modelling of gene regulatory networks identified by single cell RNA sequencing of LCs exposed to TNF-alpha, a key pro-inflammatory signal produced by the skin. Our approach delineated three programmes of LC phenotypic activation (immunogenic, tolerogenic or ambivalent), and confirmed that TNF-alpha enhanced LC immunogenic programming. Through regulon analysis followed by mutual information modelling, we identified IRF1 as the key transcription factor for the regulation of immunogenicity in LCs. Application of a mathematical toggle switch model, coupling IRF1 with tolerance-inducing transcription factors, determined the key set of transcription factors regulating the switch between tolerance and immunogenicity, and correctly predicted LC behaviour in LCs derived from different body sites. Our findings provide a mechanistic explanation of how combinatorial interactions between different transcription factors can coordinate specific transcriptional programmes in human LCs, interpreting the microenvironmental context of the local tissue microenvironments.
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Registered trials
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