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Indian hedgehog (Ihh) both promotes and restricts thymocyte differentiation

Outram, SV; Hager-Theodorides, AL; Shah, DK; Rowbotham, NJ; Drakopoulou, E; Ross, SE; Lanske, B; ... Crompton, T; + view all (2009) Indian hedgehog (Ihh) both promotes and restricts thymocyte differentiation. Blood , 113 (10) pp. 2217-2228. 10.1182/blood-2008-03-144840. Green open access

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Abstract

We show that Indian Hedgehog (Ihh) regulates T-cell development and homeostasis in both fetal and adult thymus, controlling thymocyte number. Fetal Ihh-/- thymi had reduced differentiation to double-positive (DP) cell and reduced cell numbers compared with wild-type littermates. Surprisingly, fetal Ihh+/- thymi had increased thymocyte numbers and proportion of DP cells relative to wild type, indicating that Ihh also negatively regulates thymocyte development. In vitro treatment of thymus explants with exogenous recombinant Hedgehog protein promoted thymocyte development in Ihh-/- thymi but inhibited thymocyte development in Ihh+/-, confirming both positive and negative regulatory functions of Ihh. Analysis of Rag -/-Ihh+/- thymi showed that Ihh promotes T-cell development before pre-T-cell receptor (pre-TCR) signaling, but negatively regulates T-cell development only after pre-TCR signaling has taken place. We show that Ihh is most highly expressed by the DP population and that Ihh produced by DP cells feeds back to negatively regulate the differentiation and proliferation of their double-negative progenitors. Thus, differentiation from double-negative to DP cell, and hence the size of the DP population, is dependent on the concentration of Ihh in the thymus. Analysis of Ihh conditional knockout and heterozygote adult mice showed that Ihh also influences thymocyte number in the adult. © 2009 by The American Society of Hematology.

Type: Article
Title: Indian hedgehog (Ihh) both promotes and restricts thymocyte differentiation
Open access status: An open access version is available from UCL Discovery
DOI: 10.1182/blood-2008-03-144840
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 > 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/14889
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