NADPH oxidase deficiency regulates Th lineage commitment and modulates autoimmunity

Hubert M. Tse, Terri C. Thayer, Chad Steele, Carla M. Cuda, Laurence Morel, Jon D. Piganelli, Clayton E. Mathews

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)5247-5258
Number of pages12
JournalJournal of Immunology
Volume185
Issue number9
DOIs
StatePublished - Nov 1 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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