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

CI Lau, A Barbarulo, A Solanki, JI Saldaña… - Oncotarget, 2017 - ncbi.nlm.nih.gov
CI Lau, A Barbarulo, A Solanki, JI Saldaña, T Crompton
Oncotarget, 2017ncbi.nlm.nih.gov
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 …
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.
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