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Anti-apoptotic effect of hyperglycemia can allow survival of potentially autoreactive T cells

Ramakrishnan, P. and Kahn, D. A. and Baltimore, D. (2011) Anti-apoptotic effect of hyperglycemia can allow survival of potentially autoreactive T cells. Cell Death and Differentiation, 18 (4). pp. 690-699. ISSN 1350-9047. PMCID PMC3131907.

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Thymocyte development is a tightly controlled multi-step process involving selective elimination of self-reactive and non-functional T cells by apoptosis. This developmental process depends on signaling by Notch, IL-7 and active glucose metabolism. In this study, we explored the requirement of glucose for thymocyte survival and found that in addition to metabolic regulation, glucose leads to the expression of anti-apoptotic genes. Under hyperglycemic conditions, both mouse and human thymocytes demonstrate enhanced survival. We show that glucose-induced anti-apoptotic genes are dependent on NF-κB p65 because high glucose is unable to attenuate normal ongoing apoptosis of thymocytes isolated from p65 knockout mice. Furthermore, we demonstrate that in vivo hyperglycemia decreases apoptosis of thymocytes allowing for survival of potentially self-reactive thymocytes. These results imply that hyperglycemic conditions could contribute to the development of autoimmunity through dysregulated thymic selection.

Item Type:Article
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Ramakrishnan, P.0000-0002-1314-827X
Baltimore, D.0000-0001-8723-8190
Additional Information:© 2011 Macmillan Publishers Limited. Received 21 September 2010; Revised 8 November 2010; Accepted 10 November 2010; Published online 17 December 2010. We thank the family planning division of the UCLA Department of Obstetrics and Gynecology as well as Dr. Sarah Dry of the UCLA Department of Pathology and Laboratory Medicine for assistance in isolating the human thymic tissue. c-Rel knockout animals were kindly provided by Dr. Hsiou-Chi Liou, Weill Medical College of Cornell University, New York, USA. We acknowledge the assistance Jorge Mata and Scott Washburn of the Caltech Office of Laboratory Resources. PR is supported by Supported by the National Institutes of Health 2R01GM039458 to DB. DA Kahn is supported by the National Institutes of Health Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) center at UCLA (K12 HD001400).
Funding AgencyGrant Number
NIHK12 HD001400
Subject Keywords:NF-kB; apoptosis; diabetes; T-cell development; autoimmunity
Issue or Number:4
PubMed Central ID:PMC3131907
Record Number:CaltechAUTHORS:20110401-155348899
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Official Citation:Anti-apoptotic effect of hyperglycemia can allow survival of potentially autoreactive T cells P Ramakrishnan, D A Kahn and D Baltimore Cell Death Differ 18: 690-699; advance online publication, December 17, 2010; doi:10.1038/cdd.2010.163
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:23215
Deposited By: Ruth Sustaita
Deposited On:04 Apr 2011 16:07
Last Modified:16 Apr 2020 21:06

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