Indian hedgehog (Ihh) both promotes and restricts thymocyte differentiation


Outram, SV; Hager-Theodorides, AL; Shah, DK; Rowbotham, NJ; Drakopoulou, E; Ross, SE; Lanske, B; Dessens, JT; Crompton, T; (2009) Indian hedgehog (Ihh) both promotes and restricts thymocyte differentiation. Blood, 113 (10). pp. 2217-2228. ISSN 0006-4971 DOI: https://doi.org/10.1182/blood-2008-03-144840

Full text not available from this repository.

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 (preTCR) 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. (Blood. 2009; 113: 2217-2228)

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
PubMed ID: 19109233
Web of Science ID: 263918400014
URI: http://researchonline.lshtm.ac.uk/id/eprint/5606

Statistics


Download activity - last 12 months
Downloads since deposit
0Downloads
271Hits
Accesses by country - last 12 months
Accesses by referrer - last 12 months
Impact and interest
Additional statistics for this record are available via IRStats2

Actions (login required)

Edit Item Edit Item