DR3 regulates negative selection during thymocyte development

Wang, Edward Chung Yern ORCID: https://orcid.org/0000-0002-2243-4964, Thern, Anette, Denzel, Angela, Kitson, Jeremy, Farrow, Stuart N. and Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862 2001. DR3 regulates negative selection during thymocyte development. Molecular and cellular biology 21 (10) , pp. 3451-61. 10.1128/MCB.21.10.3451-3461.2001

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Abstract

DR3 (Ws1, Apo3, LARD, TRAMP, TNFSFR12) is a member of the death domain-containing tumor necrosis factor receptor (TNFR) superfamily, members of which mediate a variety of developmental events including the regulation of cell proliferation, differentiation, and apoptosis. We have investigated the in vivo role(s) of DR3 by generating mice congenitally deficient in the expression of the DR3 gene. We show that negative selection and anti-CD3-induced apoptosis are significantly impaired in DR3-null mice. In contrast, both superantigen-induced negative selection and positive selection are normal. The pre-T-cell receptor-mediated checkpoint, which is dependent on TNFR signaling, is also unaffected in DR3-deficient mice. These data reveal a nonredundant in vivo role for this TNF receptor family member in the removal of self-reactive T cells in the thymus.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI) MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Neuroscience and Mental Health Research Institute (NMHRI)
Additional Information:	Pdf uploaded in accordance with publisher's policy at http://www.sherpa.ac.uk/romeo/issn/0270-7306/ (accessed 25/02/2014)
Publisher:	American Society for Microbiology
ISSN:	02707306
Related URLs:	http://www.ncbi.nlm.nih.gov/entrez/query...
Date of First Compliant Deposit:	30 March 2016
Last Modified:	01 Nov 2023 07:40
URI:	https://orca.cardiff.ac.uk/id/eprint/331

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