Endogenous IFN-gamma and IL-18 production directly limit induction of type 2 immunity in vivo.
Allergic diseases are associated with excessive type 2 immunity, yet the endogenous controls - if any - responsible for limiting induction of such responses remain unclear. Using IL-12-deficient mice, we recently showed that endogenous IL-12 is not essential for preventing development of allergic responses. Here, we examine the roles of endogenous IFN-gamma and IL-18 production in limiting the occurrence and severity of type 2 immunity. Lack of endogenous IFN-gamma synthesis results in significantly higher type 2 cytokine (IL-4, IL-5, IL-10 and IL-13) and chemokine (TARC) production following exogenous antigen exposure. Thus, IFN-gamma, but not IL-12, is a key negative regulator of the type 2 immune response. IL-18, in addition to its established role as an inducer of IFN-gamma, also negatively regulates CD4(+) T cell-derived IL-4 synthesis via an IFN-gamma-independent mechanism, thereby further limiting the development of type 2 immune responses. Together, these results identify endogenous IFN-gamma and IL-18 as potent, independent, negative regulators of the development of type 2 immunity to ubiquitous environmental antigens.
Lewkowich
Ian P
IP
Department of Immunology, University of Manitoba, Winnipeg, Canada.
HayGlass
Kent T
KT
D000818:Animals; D000917:Antibody Formation; D000941:Antigens / Q000008:administration & dosage; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D016207:Cytokines / Q000096:biosynthesis; D006969:Hypersensitivity, Immediate / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D018664:Interleukin-12 / Q000172:deficiency / Q000235:genetics; D020382:Interleukin-18 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
D000941:Antigens; D016207:Cytokines; D020382:Interleukin-18; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin