IFN-gamma up-regulation of IL-12 beta 2 receptor is associated with experimental autoimmune uveitis susceptible B10.A mice, but not in EAU resistant BALB/c mice.
IFN-gamma production is a hallmark of Th1 response, and IFN-gamma has multiple roles in Th1 development, depending on the experimental conditions. In this study, the correlation between IFN-gamma and interleukin 12 receptor beta2 (IL-12R beta 2) expression was investigated in experimental autoimmune uveitis (EAU) susceptible B10.A and resistant BALB/c mice. B10.A mice expressed high IL-12R beta 2 on T cells either in the disease target eyes or draining lymph node cells (LNC), and its expression correlated with the Th1-type response. In contrast, BALB/c mice only expressed minimal IL-12R beta 2 in draining LNC and had lower Th1-response. B10.A mice produced more IFN-gamma and generated a higher number of Th1 cells than that of BALB/c in the draining LNC. Furthermore, IL-12R beta 2 expression and STAT4 signaling were inhibited by anti-IFN-gamma mAb in the cultured draining LNC from B10.A mice, but enhanced by adding exogenous IFN-gamma in the cultured cells from BALB/c mice. The IL-12R beta 2 expression on Th1 cells from draining LNC was increased in the presence of IL-12 and IFN-gamma. In conclusion, IFN-gamma production correlated with IL-12R beta 2 expression on Th1-cells and IFN-gamma had a potential to regulate IL-12R beta 2 expression in vivo. This regulatory mechanism might be involved in EAU induction.
Wu
Yadi
Y
Laboratory of Molecular Immunology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, PR China.
Lin
Ying
Y
Hou
Wanqiu
W
Wang
Yanping
Y
Sun
Bing
B
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D020022:Genetic Predisposition to Disease; D007371:Interferon-gamma / Q000494:pharmacology* / Q000502:physiology; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018123:Receptors, Interleukin / Q000096:biosynthesis*; D053707:Receptors, Interleukin-12; D050797:STAT4 Transcription Factor; D015398:Signal Transduction / Q000276:immunology; D015534:Trans-Activators / Q000502:physiology; D015854:Up-Regulation / Q000276:immunology / Q000502:physiology*; D014605:Uveitis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*
D004268:DNA-Binding Proteins; C508443:Il12rb2 protein, mouse; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D050797:STAT4 Transcription Factor; C494091:Stat4 protein, mouse; D015534:Trans-Activators; D007371:Interferon-gamma