Combined deficiency of proapoptotic regulators Bim and Fas results in the early onset of systemic autoimmunity - PubMed (original) (raw)

Combined deficiency of proapoptotic regulators Bim and Fas results in the early onset of systemic autoimmunity

Jack Hutcheson et al. Immunity. 2008 Feb.

Free article

Abstract

Alterations in the stoichiometric balance between members of Bcl-2 and Fas apoptotic pathway could lead to the pathogenesis of systemic lupus erythematosus (SLE). We showed that patients with SLE displayed increased expression in antiapoptotic members of the Bcl-2 and Fas apoptotic pathways in isolated mononuclear cells. Further, mice (Bcl2l11(-/-)Fas(lpr/lpr)) lacking the Bcl-2 pro-apoptotic member, Bim (Bcl2l11(-/-)) and and with an lpr mutation in the gene encoding Fas (Fas(lpr/lpr)) developed severe SLE-like disease by 16 weeks of age unlike Bcl2l11(-/-) or Fas(lpr/lpr) mice. Bcl2l11(-/-)Fas(lpr/lpr) antigen-presenting cells (APCs) were markedly activated, and their numbers were increased in lymphoid tissues and in kidneys, yet numerous TUNEL-positive cells were observed in glomeruli of Bcl2l11(-/-)Fas(lpr/lpr) mice. These data demonstrate that dysregulation of the Bcl-2 or Fas pathways can alter the function of APCs, thereby leading to SLE pathogenesis.

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Comment in

• Fas Bim boom!
  Green DR. Green DR. Immunity. 2008 Feb;28(2):141-3. doi: 10.1016/j.immuni.2008.01.004. Immunity. 2008. PMID: 18275825

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