Interleukin-4 receptor alpha chain and STAT6 signaling inhibit gamma interferon but not Th2 cytokine expression within schistosome granulomas.
Compared to wild-type (WT) mice, schistosome granulomas in Stat6 knockout (KO) mice lacked eosinophils and had Th1 features. Interleukin-4 (IL-4) acts through Stat6 in assisting Th2 cell development. The importance of Stat6 for Th2-cell development within schistosome granulomas had not been explored. Therefore we studied gamma interferon (IFN-gamma), IL-4, and IL-5 production in granulomas from Stat6 KO and WT mice. Dispersed granuloma cells from Stat6 KO and WT mice made similar amounts of IL-4 and IL-5. Only Stat6 KO granuloma cells released IFN-gamma. Granuloma T cells contained most of the IL-4, IL-5, and IFN-gamma mRNA and secreted these cytokines. In Stat6 KO mice, 16.6% of the granuloma cells were CD4(+). Of these, 10.7% stained for IFN-gamma and/or IL-4 by intracytoplasmic flow analysis. Few CD4(-) T cells stained positively. The IL-4-producing T cells did not stain for DX5 or with labeled alpha-GalCer CD1d tetramer, suggesting an absence of NK T cells. Thus, conventional Th cells in Stat6 KO granulomas produce IFN-gamma and Th2 cytokines. Stat6 limits IFN-gamma production but is unnecessary for Th2-cell development or localization within the granuloma.
Metwali
Ahmed
A
Division of Gastroenterology-Hepatology, Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
Blum
Arthur
A
Elliott
David E
DE
Weinstock
Joel V
JV
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D006099:Granuloma / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D018664:Interleukin-12 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D015848:Interleukin-5 / Q000096:biosynthesis / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019948:Receptors, Interleukin-4 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D050800:STAT6 Transcription Factor; D012555:Schistosomiasis mansoni / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D016207:Cytokines; D015848:Interleukin-5; D012333:RNA, Messenger; D019948:Receptors, Interleukin-4; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma