Positive and negative regulatory mechanisms for fine-tuning cellularity and functions of medullary thymic epithelial cells
Self-tolerant T cells and regulatory T cells develop in the thymus. A wide variety of cell-cell interactions in the thymus is required for the differentiation, proliferation, and repertoire selection of T cells. Various secreted and cell surface molecules expressed in thymic epithelial cells mediate...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2015-09-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00461/full |
| _version_ | 1819274384707158016 |
|---|---|
| author | Taishin eAkiyama Ryosuke eTateishi Nobuko eAkiyama Riko eYoshinaga Tetsuya J. Kobayashi |
| author_facet | Taishin eAkiyama Ryosuke eTateishi Nobuko eAkiyama Riko eYoshinaga Tetsuya J. Kobayashi |
| author_sort | Taishin eAkiyama |
| collection | DOAJ |
| description | Self-tolerant T cells and regulatory T cells develop in the thymus. A wide variety of cell-cell interactions in the thymus is required for the differentiation, proliferation, and repertoire selection of T cells. Various secreted and cell surface molecules expressed in thymic epithelial cells mediate these processes. Moreover, cytokines expressed by cells of hematopoietic origin regulate the cellularity of thymic epithelial cells (TECs). Tumor necrosis factor (TNF) family RANK ligand, lymphotoxin, and CD40 ligand, expressed in T cells and innate lymphoid cells (ILCs), promote the differentiation and proliferation of medullary TECs (mTECs) that play critical roles in the induction of immune tolerance. A recent study suggests that interleukin-22 (IL-22) produced by ILCs promotes regeneration of TECs after irradiation. Intriguingly, TGF-β and osteoprotegerin limit cellularity of mTECs, thereby attenuating regulatory T cell generation. We will review recent insights into the molecular basis for cell-cell interactions regulating differentiation and proliferation of mTECs and also discuss about a perspective on use of mathematical models for understanding this complicated system. |
| first_indexed | 2024-12-23T23:07:35Z |
| format | Article |
| id | doaj.art-ed23f8c29e9042789ae1ebd305a29ab0 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-23T23:07:35Z |
| publishDate | 2015-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-ed23f8c29e9042789ae1ebd305a29ab02022-12-21T17:26:45ZengFrontiers Media S.A.Frontiers in Immunology1664-32242015-09-01610.3389/fimmu.2015.00461152645Positive and negative regulatory mechanisms for fine-tuning cellularity and functions of medullary thymic epithelial cellsTaishin eAkiyama0Ryosuke eTateishi1Nobuko eAkiyama2Riko eYoshinaga3Tetsuya J. Kobayashi4University of TokyoUniversity of TokyoUniversity of TokyoUniversity of TokyoInstitute of Industrial Science, The University of TokyoSelf-tolerant T cells and regulatory T cells develop in the thymus. A wide variety of cell-cell interactions in the thymus is required for the differentiation, proliferation, and repertoire selection of T cells. Various secreted and cell surface molecules expressed in thymic epithelial cells mediate these processes. Moreover, cytokines expressed by cells of hematopoietic origin regulate the cellularity of thymic epithelial cells (TECs). Tumor necrosis factor (TNF) family RANK ligand, lymphotoxin, and CD40 ligand, expressed in T cells and innate lymphoid cells (ILCs), promote the differentiation and proliferation of medullary TECs (mTECs) that play critical roles in the induction of immune tolerance. A recent study suggests that interleukin-22 (IL-22) produced by ILCs promotes regeneration of TECs after irradiation. Intriguingly, TGF-β and osteoprotegerin limit cellularity of mTECs, thereby attenuating regulatory T cell generation. We will review recent insights into the molecular basis for cell-cell interactions regulating differentiation and proliferation of mTECs and also discuss about a perspective on use of mathematical models for understanding this complicated system.http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00461/fullT cellsmathematical modelingautoimmune diseaseThymusnegative feedbackMedullary thymic epitheilal cells |
| spellingShingle | Taishin eAkiyama Ryosuke eTateishi Nobuko eAkiyama Riko eYoshinaga Tetsuya J. Kobayashi Positive and negative regulatory mechanisms for fine-tuning cellularity and functions of medullary thymic epithelial cells Frontiers in Immunology T cells mathematical modeling autoimmune disease Thymus negative feedback Medullary thymic epitheilal cells |
| title | Positive and negative regulatory mechanisms for fine-tuning cellularity and functions of medullary thymic epithelial cells |
| title_full | Positive and negative regulatory mechanisms for fine-tuning cellularity and functions of medullary thymic epithelial cells |
| title_fullStr | Positive and negative regulatory mechanisms for fine-tuning cellularity and functions of medullary thymic epithelial cells |
| title_full_unstemmed | Positive and negative regulatory mechanisms for fine-tuning cellularity and functions of medullary thymic epithelial cells |
| title_short | Positive and negative regulatory mechanisms for fine-tuning cellularity and functions of medullary thymic epithelial cells |
| title_sort | positive and negative regulatory mechanisms for fine tuning cellularity and functions of medullary thymic epithelial cells |
| topic | T cells mathematical modeling autoimmune disease Thymus negative feedback Medullary thymic epitheilal cells |
| url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00461/full |
| work_keys_str_mv | AT taishineakiyama positiveandnegativeregulatorymechanismsforfinetuningcellularityandfunctionsofmedullarythymicepithelialcells AT ryosukeetateishi positiveandnegativeregulatorymechanismsforfinetuningcellularityandfunctionsofmedullarythymicepithelialcells AT nobukoeakiyama positiveandnegativeregulatorymechanismsforfinetuningcellularityandfunctionsofmedullarythymicepithelialcells AT rikoeyoshinaga positiveandnegativeregulatorymechanismsforfinetuningcellularityandfunctionsofmedullarythymicepithelialcells AT tetsuyajkobayashi positiveandnegativeregulatorymechanismsforfinetuningcellularityandfunctionsofmedullarythymicepithelialcells |