The kinesin motor protein Kif7 is required for T-cell development and normal MHC expression on thymic epithelial cells (TEC) in the thymus

Article


Lau, Ching-In, Barbarulo, Alessandro, Solanki, Anisha, Saldaña, J. and Crompton, Tessa 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.
AuthorsLau, Ching-In, Barbarulo, Alessandro, Solanki, Anisha, Saldaña, J. and Crompton, Tessa
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.

KeywordsKif7; T-cell development; thymus; thymic epithelial cell; sonic hedgehog; Immunology and Microbiology Section; Immune response; Immunity
JournalOncotarget
Journal citation8 (15), pp. 24163-24176
ISSN1949-2553
Year2017
PublisherImpact Journals
Publisher's version
License
CC BY
Digital Object Identifier (DOI)doi:10.18632/oncotarget.15241
Publication dates
Print09 Feb 2017
Publication process dates
Deposited15 May 2017
Accepted21 Jan 2017
FunderMedical Research Council
Biotechnology and Biological Sciences Research Council (BBSRC)
Wellcome Trust
Great Ormond Street Hospital Children’s Charity
National Institute for Health Research Biomedical Research Centre
ISTITUTO PASTEUR ITALIA Fondazione Cenci Bolognetti
Medical Research Council
Biotechnology and Biological Sciences Research Council
Wellcome Trust
Great Ormond Street Hospital Charity
National Institute for Health Research
Istituto Pasteur-Fondazione Cenci Bolognetti
Copyright information© The authors 2017. 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.
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