NADPH oxidase deficiency regulates Th lineage commitment and modulates autoimmunity

Academic Article

Abstract

  • Reactive oxygen species are used by the immune system to eliminate infections; however, they may also serve as signaling intermediates to coordinate the efforts of the innate and adaptive immune systems. In this study, we show that by eliminating macrophage and T cell superoxide production through the NADPH oxidase (NOX), T cell polarization was altered. After stimulation with immobilized anti-CD3 and anti-CD28 or priming recall, T cells from NOX-deficient mice exhibited a skewed Th17 phenotype, whereas NOX-intact cells produced cytokines indicative of a Th1 response. These findings were corroborated in vivo by studying two different autoimmune diseases mediated by Th17 or Th1 pathogenic T cell responses. NOX-deficient NOD mice were Th17 prone with a concomitant susceptibility to experimental allergic encephalomyelitis and significant protection against type 1 diabetes. These data validate the role of superoxide in shaping Th responses and as a signaling intermediate to modulate Th17 and Th1 T cell responses. Copyright © 2010 by The American Association of Immunologists, Inc.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Tse HM; Thayer TC; Steele C; Cuda CM; Morel L; Piganelli JD; Mathews CE
  • Start Page

  • 5247
  • End Page

  • 5258
  • Volume

  • 185
  • Issue

  • 9