A20 Restrains Thymic Regulatory T Cell Development
| العنوان: | A20 Restrains Thymic Regulatory T Cell Development |
|---|---|
| المؤلفون: | Simon Heidegger, Julius C. Fischer, Christian Peschel, Maike Kober, Xian Chang Li, Marc Schmidt-Supprian, Vera Otten, Hendrik Poeck, Marc Rosenbaum, Christoph Drees, Tobias Haas, Silvia Spoerl, Martina Schmickl, Geert van Loo, Rudi Beyaert |
| المصدر: | Journal of immunology (Baltimore, Md. : 1950) |
| بيانات النشر: | The American Association of Immunologists, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | CD4-Positive T-Lymphocytes, 0301 basic medicine, Regulatory T cell, T cell, Immunology, Graft vs Host Disease, Apoptosis, chemical and pharmacologic phenomena, Thymus Gland, Biology, Lymphocyte Activation, T-Lymphocytes, Regulatory, Article, Immune tolerance, Mice, 03 medical and health sciences, 0302 clinical medicine, Glucocorticoid-Induced TNFR-Related Protein, hemic and lymphatic diseases, medicine, Animals, Immunology and Allergy, Cytotoxic T cell, IL-2 receptor, Antigen-presenting cell, Tumor Necrosis Factor alpha-Induced Protein 3, NF-kappa B, Transcription Factor RelA, FOXP3, Cell Differentiation, Forkhead Transcription Factors, hemic and immune systems, Flow Cytometry, Natural killer T cell, Proto-Oncogene Proteins c-rel, Cell biology, 030104 developmental biology, medicine.anatomical_structure, Gene Expression Regulation, Interleukin-2, Signal Transduction, Stem Cell Transplantation, 030215 immunology |
| الوصف: | Maintaining immune tolerance requires the production of Foxp3-expressing regulatory T (Treg) cells in the thymus. Activation of NF-κB transcription factors is critically required for Treg cell development, partly via initiating Foxp3 expression. NF-κB activation is controlled by a negative feedback regulation through the ubiquitin editing enzyme A20, which reduces proinflammatory signaling in myeloid cells and B cells. In naive CD4+ T cells, A20 prevents kinase RIPK3-dependent necroptosis. Using mice deficient for A20 in T lineage cells, we show that thymic and peripheral Treg cell compartments are quantitatively enlarged because of a cell-intrinsic developmental advantage of A20-deficient thymic Treg differentiation. A20-deficient thymic Treg cells exhibit reduced dependence on IL-2 but unchanged rates of proliferation and apoptosis. Activation of the NF-κB transcription factor RelA was enhanced, whereas nuclear translocation of c-Rel was decreased in A20-deficient thymic Treg cells. Furthermore, we found that the increase in Treg cells in T cell–specific A20-deficient mice was already observed in CD4+ single-positive CD25+ GITR+ Foxp3− thymic Treg cell progenitors. Treg cell precursors expressed high levels of the tumor necrosis factor receptor superfamily molecule GITR, whose stimulation is closely linked to thymic Treg cell development. A20-deficient Treg cells efficiently suppressed effector T cell–mediated graft-versus-host disease after allogeneic hematopoietic stem cell transplantation, suggesting normal suppressive function. Holding thymic production of natural Treg cells in check, A20 thus integrates Treg cell activity and increased effector T cell survival into an efficient CD4+ T cell response. |
| تدمد: | 1550-6606 0022-1767 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5895237111b068380b8e5aadd81ebb5dTest https://doi.org/10.4049/jimmunol.1602102Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5895237111b068380b8e5aadd81ebb5d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
|---|