SHP1-ing thymic selection

Thymocyte development and maintenance of peripheral T-cell numbers and functions are critically dependent on T-cell receptor (TCR) signal strength. SHP1 (Src homology region 2 domain-containing phosphatase-1), a tyrosine phosphatase, acts as a negative regulator of TCR signal strength. Moreover, ger...

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Main Authors: Gascoigne, N, Brzostek, J, Mehta, M, Acuto, O
格式: Journal article
语言:English
出版: John Wiley and Sons, Inc 2016
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author Gascoigne, N
Brzostek, J
Mehta, M
Acuto, O
author_facet Gascoigne, N
Brzostek, J
Mehta, M
Acuto, O
author_sort Gascoigne, N
collection OXFORD
description Thymocyte development and maintenance of peripheral T-cell numbers and functions are critically dependent on T-cell receptor (TCR) signal strength. SHP1 (Src homology region 2 domain-containing phosphatase-1), a tyrosine phosphatase, acts as a negative regulator of TCR signal strength. Moreover, germline SHP1 knockout mice have shown impaired thymic development. However, this has been recently questioned by an analysis of SHP1 conditional knockout mice, which reported normal thymic development of SHP1 deficient thymocytes. Using this SHP1 conditional knockout mice, in this issue of the European Journal of Immunology, Martinez et al. [Eur. J. Immunol. 2016. 46: 2103-2110] show that SHP1 indeed does have a role in the negative regulation of TCR signal strength in positively selected thymocytes, and in the final maturation of single positive thymocytes. They report that thymocyte development in such mice shows loss of mature, post-selection cells. This is due to increased TCR signal transduction in thymocytes immediately post positive-selection, and increased cell death in response to weak TCR ligands. Thus, SHP1-deficiency shows strong similarities to deficiency in the T-cell specific SHP1-associated protein Themis.
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spelling oxford-uuid:d343b1f3-81c4-4076-9552-317ac07fbbed2022-03-27T08:10:06ZSHP1-ing thymic selectionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d343b1f3-81c4-4076-9552-317ac07fbbedEnglishSymplectic Elements at OxfordJohn Wiley and Sons, Inc2016Gascoigne, NBrzostek, JMehta, MAcuto, OThymocyte development and maintenance of peripheral T-cell numbers and functions are critically dependent on T-cell receptor (TCR) signal strength. SHP1 (Src homology region 2 domain-containing phosphatase-1), a tyrosine phosphatase, acts as a negative regulator of TCR signal strength. Moreover, germline SHP1 knockout mice have shown impaired thymic development. However, this has been recently questioned by an analysis of SHP1 conditional knockout mice, which reported normal thymic development of SHP1 deficient thymocytes. Using this SHP1 conditional knockout mice, in this issue of the European Journal of Immunology, Martinez et al. [Eur. J. Immunol. 2016. 46: 2103-2110] show that SHP1 indeed does have a role in the negative regulation of TCR signal strength in positively selected thymocytes, and in the final maturation of single positive thymocytes. They report that thymocyte development in such mice shows loss of mature, post-selection cells. This is due to increased TCR signal transduction in thymocytes immediately post positive-selection, and increased cell death in response to weak TCR ligands. Thus, SHP1-deficiency shows strong similarities to deficiency in the T-cell specific SHP1-associated protein Themis.
spellingShingle Gascoigne, N
Brzostek, J
Mehta, M
Acuto, O
SHP1-ing thymic selection
title SHP1-ing thymic selection
title_full SHP1-ing thymic selection
title_fullStr SHP1-ing thymic selection
title_full_unstemmed SHP1-ing thymic selection
title_short SHP1-ing thymic selection
title_sort shp1 ing thymic selection
work_keys_str_mv AT gascoignen shp1ingthymicselection
AT brzostekj shp1ingthymicselection
AT mehtam shp1ingthymicselection
AT acutoo shp1ingthymicselection