NADPH oxidase deficiency regulates Th lineage commitment and modulates autoimmunity.
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.
Tse
Hubert M
HM
Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA.
Thayer
Terri C
TC
Steele
Chad
C
Cuda
Carla M
CM
Morel
Laurence
L
Piganelli
Jon D
JD
Mathews
Clayton E
CE
D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D015153:Blotting, Western; D019070:Cell Lineage / Q000276:immunology*; D002469:Cell Separation; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D020381:Interleukin-17 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D019255:NADPH Oxidases / Q000172:deficiency* / Q000276:immunology; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013481:Superoxides / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000201:enzymology / Q000276:immunology
D016207:Cytokines; D020381:Interleukin-17; D017382:Reactive Oxygen Species; D013481:Superoxides; D019255:NADPH Oxidases