ArticleJournal of autoimmunity2015
Natural Th17 cells are critically regulated by functional medullary thymic microenvironments.
Article in Journal of autoimmunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- T Cell Thoughts.Immunological reviews · 2026Review
- Sex-specific differences in ICOSClinical and experimental medicine · 2024Article
- S1PR1 mediates Th17 cell migration from the thymus to the skin in health and disease.Frontiers in immunology · 2024Article
- Impaired Differentiation of Highly Proliferative ICOSInternational journal of molecular sciences · 2021Article
- Recognition ofMicroorganisms · 2020Review
- Biological characteristics of transcription factor RelB in different immune cell types: implications for the treatment of multiple sclerosis.Molecular brain · 2019Review
- Invariant NKT Cells and Control of the Thymus Medulla.Journal of immunology (Baltimore, Md. : 1950) · 2018Review
- Twenty Years of AIRE.Frontiers in immunology · 2018Review
- Redefining thymus medulla specialization for central tolerance.The Journal of experimental medicine · 2017Article
- Precocious Interleukin 21 Expression in Naive Mice Identifies a Natural Helper Cell Population in Autoimmune Disease.Cell reports · 2017Article
- T-Bet independent development of IFNγ secreting natural T helper 1 cell population in the absence of Itk.Scientific reports · 2017Article
- Control of the thymic medulla and its influence on αβT-cell development.Immunological reviews · 2016Review
- Development of interleukin-17-producing Vγ2+ γδ T cells is reduced by ICOS signaling in the thymus.Oncotarget · 2016Article
- Thymic stromal cell subsets for T cell development.Cellular and molecular life sciences : CMLS · 2016Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The thymic medulla is critical for the enforcement of central tolerance. In addition to deletion of auto-reactive T-cells, the thymic medulla supports the maturation of heterogeneous natural αβT-cells linked to tolerance mechanisms. Natural IL-17-secreting CD4(+)αβT-cells (nTh17) represent recently described natural αβT-cells that mature and undergo functional priming intrathymically. Despite a proposed potential to impact upon either protective or pathological inflammatory responses, the intrathymic mechanisms regulating the balance of nTh17 development are unclear. Here we compare the development of distinct natural αβT-cells in the thymus. We reveal that thymic stromal MHC class II expression and RelB-dependent medullary thymic epithelial cells (mTEC), including Aire(+) mTEC, are an essential requirement for nTh17 development. nTh17 demonstrate a partial, non-redundant requirement for both ICOS-ligand and CD80/86 costimulation, with a dispensable role for CD80/86 expression by thymic epithelial cells. Although mTEC constitutively expressed inducible nitric oxide synthase (iNOS), a critical negative regulator of conventional Th17 differentiation, iNOS was not essential to constrain thymic nTh17. These findings highlight the critical role of the thymic medulla in the differential regulation of novel natural αβT-cell subsets, and reveal additional layers of thymic medullary regulation of T-cell driven autoimmunity and inflammation.
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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.