Roles of Bcl-3 in the pathogenesis of murine type 1 diabetes.

Diabetes
Qingguo RuanYouhai H Chen

Abstract

It has long been recognized that autoimmunity is often associated with immunodeficiency. The mechanism underlying this paradox is not well understood. Bcl-3 (B-cell lymphoma 3) is an atypical member of the IκB (inhibitor of the nuclear factor-κB) family that is required for lymphoid organogenesis and germinal center responses. Mice deficient in Bcl-3 are immunodeficient because of the microarchitectural defects of their lymphoid organs. The goal of this study is to define the potential roles of Bcl-3 in type 1 diabetes. Bcl-3-deficient NOD mice were generated by backcrossing Bcl-3-deficient C57BL/6 mice to NOD mice. Spontaneous and induced type 1 diabetes were studied in these mice by both pathologic and immunologic means. The effect of Bcl-3 on inflammatory gene transcription was evaluated in a promoter reporter assay. We found that Bcl-3-deficient NOD and C57BL/6 mice were, paradoxically, more susceptible to autoimmune diabetes than wild-type mice. The increase in diabetes susceptibility was caused by Bcl-3 deficiency in hematopoietic cells but not nonhematopoietic cells. Bcl-3 deficiency did not significantly affect anti-islet Th1 or Th2 autoimmune responses, but markedly increased inflammatory chemokine and T helper 17 (Th1...Continue Reading

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Citations

Nov 5, 2010·Journal of Proteome Research·Hyun-Jin KimSuk Hoo Yoon
Oct 16, 2010·Metabolic Syndrome and Related Disorders·Pavani Bandaru, Anoop Shankar
Apr 13, 2013·Cell Communication and Signaling : CCS·Marc SchusterIngo Schmitz
Jul 12, 2012·Journal of Leukocyte Biology·Shashi BalaGyongyi Szabo
Jan 26, 2016·Immunology Letters·Michaela AnnemannIngo Schmitz
Feb 25, 2015·European Journal of Immunology·Heike Weighardt, Irmgard Förster
Mar 31, 2016·Cells·Felicity D Herrington, Robert J B Nibbs
Nov 19, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xiaoren ZhangUlrich Siebenlist
Jan 14, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Frédéric PèneUlrich Siebenlist
Jul 12, 2020·European Journal of Immunology·Wanhu TangUlrich Siebenlist
Sep 24, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ilaria TassiUlrich Siebenlist
Feb 2, 2021·Immunology and Cell Biology·Wanhu TangUlrich Siebenlist

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Methods Mentioned

BETA
PCR
flow cytometry
ELISA
transfection
transgenic
PMA

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