Lau, C-I;
Barbarulo, A;
Solanki, A;
Saldana, JI;
Crompton, T;
(2017)
The kinesin motor protein Kif7 is required for T-cell development and normal MHC expression on thymic epithelial cells (TEC) in the thymus.
Oncotarget
, 8
(15)
pp. 24163-24176.
10.18632/oncotarget.15241.
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The kinesin motor protein Kif7 is required for T-cell development and normal MHC expression on thymic epithelial cells (TEC) in the thymus.pdf - Published Version Download (5MB) | Preview |
Abstract
Kif7 is a ciliary kinesin motor protein that regulates mammalian Hedgehog pathway activation through influencing structure of the primary cilium. Here we show that Kif7 is required for normal T-cell development, despite the fact that T-cells lack primary cilia. Analysis of Kif7-deficient thymus showed that Kif7-deficiency increases the early CD44+CD25+CD4-CD8- thymocyte progenitor population but reduces differentiation to CD4+CD8+ double positive (DP) cell. At the transition from DP to mature T-cell, Kif7-deficiency selectively delayed maturation to the CD8 lineage. Expression of CD5, which correlates with TCR signal strength, was reduced on DP and mature CD4 and CD8 cells, as a result of thymocyte-intrinsic Kif7-deficiency, and Kif7-deficient T-cells from radiation chimeras activated less efficiently when stimulated with anti-CD3 and anti-CD28 in vitro. Kif7-deficient thymocytes showed higher expression of the Hedgehog target gene Ptch1 than WT, but were less sensitive to treatment with recombinant Shh, and Kif7-deficient T-cell development was refractory to neutralisation of endogenous Hh proteins, indicating that Kif7-deficient thymocytes were unable to interpret changes in the Hedgehog signal. In addition, Kif7-deficiency reduced cell-surface MHCII expression on thymic epithelial cells.
| Type: | Article |
|---|---|
| Title: | The kinesin motor protein Kif7 is required for T-cell development and normal MHC expression on thymic epithelial cells (TEC) in the thymus |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.18632/oncotarget.15241 |
| Publisher version: | http://dx.doi.org/10.18632/oncotarget.15241 |
| Language: | English |
| Additional information: | Copyright: Lau et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Oncology, Cell Biology, Kif7, T-cell development, thymus, thymic epithelial cell, sonic hedgehog, Immunology and Microbiology Section, Immune response, Immunity, HEDGEHOG SIGNAL-TRANSDUCTION, THYMOCYTE DEVELOPMENT, REGULATES DIFFERENTIATION, POSITIVE THYMOCYTE, ACTIVATION, COMPLEX, DROSOPHILA, MECHANISM, SELECTION, CD5 |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1556939 |
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