ArticleThe Journal of experimental medicine2010
Regulation of medullary thymic epithelial cell differentiation and function by the signaling protein Sin.
Article in The Journal of experimental medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- TOX deficiency facilitates the differentiation of IL-17A-producing γδ T cells to drive autoimmune hepatitis.Cellular & molecular immunology · 2022Article
- Epithelial Fli1 deficiency drives systemic autoimmunity and fibrosis: Possible roles in scleroderma.The Journal of experimental medicine · 2017Article
- Restoration of Thymus Function with Bioengineered Thymus Organoids.Current stem cell reports · 2016Article
- Embryonal Fyn-associated substrate (EFS) and CASS4: The lesser-known CAS protein family members.Gene · 2015Review
- Thymus medulla fosters generation of natural Treg cells, invariant γδ T cells, and invariant NKT cells: what we learn from intrathymic migration.European journal of immunology · 2015Review
- CAS proteins in health and disease: an update.IUBMB life · 2014Review
- Identification of novel thymic epithelial cell subsets whose differentiation is regulated by RANKL and Traf6.PloS one · 2014Article
- Medullary thymic epithelial cell depletion leads to autoimmune hepatitis.The Journal of clinical investigation · 2013Article
- Thymic epithelial cell development and differentiation: cellular and molecular regulation.Protein & cell · 2013Review
- Potential link between MHC-self-peptide presentation and hematopoiesis; the analysis of HLA-DR expression in CD34-positive cells and self-peptide presentation repertoires of MHC molecules associated with paroxysmal nocturnal hemoglobinuria.Cell biochemistry and biophysics · 2013Article
- Regulations of gene expression in medullary thymic epithelial cells required for preventing the onset of autoimmune diseases.Frontiers in immunology · 2013Article
- Maturation and emigration of single-positive thymocytes.Clinical & developmental immunology · 2013Review
- Thymic epithelial cells: antigen presenting cells that regulate T cell repertoire and tolerance development.Immunologic research · 2012Review
- Age-Related Disruption of Steady-State Thymic Medulla Provokes Autoimmune Phenotype via Perturbing Negative Selection.Aging and disease · 2012Article
- Expression of the autoimmune regulator gene and its relevance to the mechanisms of central and peripheral tolerance.Clinical & developmental immunology · 2012Review
- EFS shows biallelic methylation in uveal melanoma with poor prognosis as well as tissue-specific methylation.BMC cancer · 2011Article
- Control of central and peripheral tolerance by Aire.Immunological reviews · 2011Review
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Authors and funding
3 authors.
Funding
Abstract
Medullary thymic epithelial cells (mTECs) play an important role in T cell tolerance and prevention of autoimmunity. Mice deficient in expression of the signaling protein Sin exhibit exaggerated immune responses and multitissue inflammation. Here, we show that Sin is expressed in the thymic stroma, specifically in mTECs. Sin deficiency led to thymic stroma-dependent autoimmune manifestations shown by radiation chimeras and thymic transplants in nude mice, and associated with defective mTEC-mediated elimination of thymocytes in a T cell receptor transgenic model of negative selection. Lack of Sin expression correlated with a disorganized medullary architecture and fewer functionally mature mTECs under steady-state conditions. Additionally, Sin deficiency inhibited the expansion of mTECs in response to in vivo administration of keratinocyte growth factor (KGF). These results identify Sin as a novel regulator of mTEC development and T cell tolerance, and suggest that Sin is important for homeostatic maintenance of the medullary epithelium in the adult thymus.
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