Strong TCRγδ Signaling Prohibits Thymic Development of IL-17A-Secreting γδ T Cells
Summary: Despite a growing appreciation of γδ T cell contributions to numerous immune responses, the mechanisms that underpin their thymic development remain poorly understood. Here, using precursor/product relationships, we identify thymic stages in two distinct developmental pathways that generate...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2017-06-01
|
| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717307283 |
| _version_ | 1828482112483753984 |
|---|---|
| author | Nital Sumaria Capucine L. Grandjean Bruno Silva-Santos Daniel J. Pennington |
| author_facet | Nital Sumaria Capucine L. Grandjean Bruno Silva-Santos Daniel J. Pennington |
| author_sort | Nital Sumaria |
| collection | DOAJ |
| description | Summary: Despite a growing appreciation of γδ T cell contributions to numerous immune responses, the mechanisms that underpin their thymic development remain poorly understood. Here, using precursor/product relationships, we identify thymic stages in two distinct developmental pathways that generate γδ T cells pre-committed to subsequent secretion of either IL-17A or IFNγ. Importantly, this framework for tracking γδ T cell development has permitted definitive assessment of TCRγδ signal strength in commitment to γδ T cell effector fate; increased TCRγδ signal strength profoundly prohibited the development of all IL-17A-secreting γδ T cells, regardless of Vγ usage, but promoted the development of γδ progenitors along the IFNγ pathway. This clarifies the recently debated role of TCRγδ signal strength in commitment to distinct γδ T cell effector fates and proposes an alternate methodology for the study of γδ T cell development. : Sumaria et al. identify distinct thymic pathways that generate murine γδ T cells pre-committed to the secretion of IL-17A or IFNγ. This permits assessment of TCRγδ signal strength in thymic commitment to γδ T cell effector fate; increased TCRγδ signal strength profoundly prohibits development of all IL-17A-secreting γδ T cells. Keywords: murine γδ T cells, T cell development, TCRγδ signal strength, IL-17A |
| first_indexed | 2024-12-11T08:08:35Z |
| format | Article |
| id | doaj.art-5de5b18478854e8dbe5579a70db71df6 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-11T08:08:35Z |
| publishDate | 2017-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-5de5b18478854e8dbe5579a70db71df62022-12-22T01:14:56ZengElsevierCell Reports2211-12472017-06-01191224692476Strong TCRγδ Signaling Prohibits Thymic Development of IL-17A-Secreting γδ T CellsNital Sumaria0Capucine L. Grandjean1Bruno Silva-Santos2Daniel J. Pennington3Blizard Institute, Barts and The London School of Medicine, Queen Mary University of London, 4 Newark Street, London E1 2AT, UKBlizard Institute, Barts and The London School of Medicine, Queen Mary University of London, 4 Newark Street, London E1 2AT, UKInstituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1600-276 Lisboa, PortugalBlizard Institute, Barts and The London School of Medicine, Queen Mary University of London, 4 Newark Street, London E1 2AT, UK; Corresponding authorSummary: Despite a growing appreciation of γδ T cell contributions to numerous immune responses, the mechanisms that underpin their thymic development remain poorly understood. Here, using precursor/product relationships, we identify thymic stages in two distinct developmental pathways that generate γδ T cells pre-committed to subsequent secretion of either IL-17A or IFNγ. Importantly, this framework for tracking γδ T cell development has permitted definitive assessment of TCRγδ signal strength in commitment to γδ T cell effector fate; increased TCRγδ signal strength profoundly prohibited the development of all IL-17A-secreting γδ T cells, regardless of Vγ usage, but promoted the development of γδ progenitors along the IFNγ pathway. This clarifies the recently debated role of TCRγδ signal strength in commitment to distinct γδ T cell effector fates and proposes an alternate methodology for the study of γδ T cell development. : Sumaria et al. identify distinct thymic pathways that generate murine γδ T cells pre-committed to the secretion of IL-17A or IFNγ. This permits assessment of TCRγδ signal strength in thymic commitment to γδ T cell effector fate; increased TCRγδ signal strength profoundly prohibits development of all IL-17A-secreting γδ T cells. Keywords: murine γδ T cells, T cell development, TCRγδ signal strength, IL-17Ahttp://www.sciencedirect.com/science/article/pii/S2211124717307283 |
| spellingShingle | Nital Sumaria Capucine L. Grandjean Bruno Silva-Santos Daniel J. Pennington Strong TCRγδ Signaling Prohibits Thymic Development of IL-17A-Secreting γδ T Cells Cell Reports |
| title | Strong TCRγδ Signaling Prohibits Thymic Development of IL-17A-Secreting γδ T Cells |
| title_full | Strong TCRγδ Signaling Prohibits Thymic Development of IL-17A-Secreting γδ T Cells |
| title_fullStr | Strong TCRγδ Signaling Prohibits Thymic Development of IL-17A-Secreting γδ T Cells |
| title_full_unstemmed | Strong TCRγδ Signaling Prohibits Thymic Development of IL-17A-Secreting γδ T Cells |
| title_short | Strong TCRγδ Signaling Prohibits Thymic Development of IL-17A-Secreting γδ T Cells |
| title_sort | strong tcrγδ signaling prohibits thymic development of il 17a secreting γδ t cells |
| url | http://www.sciencedirect.com/science/article/pii/S2211124717307283 |
| work_keys_str_mv | AT nitalsumaria strongtcrgdsignalingprohibitsthymicdevelopmentofil17asecretinggdtcells AT capucinelgrandjean strongtcrgdsignalingprohibitsthymicdevelopmentofil17asecretinggdtcells AT brunosilvasantos strongtcrgdsignalingprohibitsthymicdevelopmentofil17asecretinggdtcells AT danieljpennington strongtcrgdsignalingprohibitsthymicdevelopmentofil17asecretinggdtcells |