CD8+ Tc2 cells: underappreciated contributors to severe asthma
The complexity of asthma is underscored by the number of cell types and mediators implicated in the pathogenesis of this heterogeneous syndrome. Type 2 CD4+ T-cells (Th2) and more recently, type 2 innate lymphoid cells dominate current descriptions of asthma pathogenesis. However, another important...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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European Respiratory Society
2019-11-01
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| Series: | European Respiratory Review |
| Online Access: | http://err.ersjournals.com/content/28/154/190092.full |
| _version_ | 1819105752051089408 |
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| author | Timothy S.C. Hinks Ryan D. Hoyle Erwin W. Gelfand |
| author_facet | Timothy S.C. Hinks Ryan D. Hoyle Erwin W. Gelfand |
| author_sort | Timothy S.C. Hinks |
| collection | DOAJ |
| description | The complexity of asthma is underscored by the number of cell types and mediators implicated in the pathogenesis of this heterogeneous syndrome. Type 2 CD4+ T-cells (Th2) and more recently, type 2 innate lymphoid cells dominate current descriptions of asthma pathogenesis. However, another important source of these type 2 cytokines, especially interleukin (IL)-5 and IL-13, are CD8+ T-cells, which are increasingly proposed to play an important role in asthma pathogenesis, because they are abundant and are comparatively insensitive to corticosteroids. Many common triggers of asthma exacerbations are mediated via corticosteroid-resistant pathways involving neutrophils and CD8+ T-cells. Extensive murine data reveal the plasticity of CD8+ T-cells and their capacity to enhance airway inflammation and airway dysfunction. In humans, Tc2 cells are predominant in fatal asthma, while in stable state, severe eosinophilic asthma is associated with greater numbers of Tc2 than Th2 cells in blood, bronchoalveolar lavage fluid and bronchial biopsies. Tc2 cells strongly express CRTH2, the receptor for prostaglandin D2, the cysteinyl leukotriene receptor 1 and the leukotriene B4 receptor. When activated, these elicit Tc2 cell chemotaxis and production of chemokines and type 2 and other cytokines, resulting directly or indirectly in eosinophil recruitment and survival. These factors position CD8+ Tc2 cells as important and underappreciated effector cells contributing to asthma pathogenesis. Here, we review recent advances and new insights in understanding the pro-asthmatic functions of CD8+ T-cells in eosinophilic asthma, especially corticosteroid-resistant asthma, and the molecular mechanisms underlying their pathologic effector function. |
| first_indexed | 2024-12-22T02:27:14Z |
| format | Article |
| id | doaj.art-2f0a377e9c96415c9778d3b54907d6ad |
| institution | Directory Open Access Journal |
| issn | 0905-9180 1600-0617 |
| language | English |
| last_indexed | 2024-12-22T02:27:14Z |
| publishDate | 2019-11-01 |
| publisher | European Respiratory Society |
| record_format | Article |
| series | European Respiratory Review |
| spelling | doaj.art-2f0a377e9c96415c9778d3b54907d6ad2022-12-21T18:41:58ZengEuropean Respiratory SocietyEuropean Respiratory Review0905-91801600-06172019-11-012815410.1183/16000617.0092-20190092-2019CD8+ Tc2 cells: underappreciated contributors to severe asthmaTimothy S.C. Hinks0Ryan D. Hoyle1Erwin W. Gelfand2 Respiratory Medicine Unit and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), Nuffield Dept of Medicine Experimental Medicine, University of Oxford, Oxford, UK Respiratory Medicine Unit and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), Nuffield Dept of Medicine Experimental Medicine, University of Oxford, Oxford, UK Division of Cell Biology, Dept of Pediatrics, National Jewish Health, Denver, CO, USA The complexity of asthma is underscored by the number of cell types and mediators implicated in the pathogenesis of this heterogeneous syndrome. Type 2 CD4+ T-cells (Th2) and more recently, type 2 innate lymphoid cells dominate current descriptions of asthma pathogenesis. However, another important source of these type 2 cytokines, especially interleukin (IL)-5 and IL-13, are CD8+ T-cells, which are increasingly proposed to play an important role in asthma pathogenesis, because they are abundant and are comparatively insensitive to corticosteroids. Many common triggers of asthma exacerbations are mediated via corticosteroid-resistant pathways involving neutrophils and CD8+ T-cells. Extensive murine data reveal the plasticity of CD8+ T-cells and their capacity to enhance airway inflammation and airway dysfunction. In humans, Tc2 cells are predominant in fatal asthma, while in stable state, severe eosinophilic asthma is associated with greater numbers of Tc2 than Th2 cells in blood, bronchoalveolar lavage fluid and bronchial biopsies. Tc2 cells strongly express CRTH2, the receptor for prostaglandin D2, the cysteinyl leukotriene receptor 1 and the leukotriene B4 receptor. When activated, these elicit Tc2 cell chemotaxis and production of chemokines and type 2 and other cytokines, resulting directly or indirectly in eosinophil recruitment and survival. These factors position CD8+ Tc2 cells as important and underappreciated effector cells contributing to asthma pathogenesis. Here, we review recent advances and new insights in understanding the pro-asthmatic functions of CD8+ T-cells in eosinophilic asthma, especially corticosteroid-resistant asthma, and the molecular mechanisms underlying their pathologic effector function.http://err.ersjournals.com/content/28/154/190092.full |
| spellingShingle | Timothy S.C. Hinks Ryan D. Hoyle Erwin W. Gelfand CD8+ Tc2 cells: underappreciated contributors to severe asthma European Respiratory Review |
| title | CD8+ Tc2 cells: underappreciated contributors to severe asthma |
| title_full | CD8+ Tc2 cells: underappreciated contributors to severe asthma |
| title_fullStr | CD8+ Tc2 cells: underappreciated contributors to severe asthma |
| title_full_unstemmed | CD8+ Tc2 cells: underappreciated contributors to severe asthma |
| title_short | CD8+ Tc2 cells: underappreciated contributors to severe asthma |
| title_sort | cd8 tc2 cells underappreciated contributors to severe asthma |
| url | http://err.ersjournals.com/content/28/154/190092.full |
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