title: Critical role of the endogenous interferon ligand-receptors in type I and type II interferons response.
abstract: Separate ligand-receptor paradigms are commonly used for each type of interferon (IFN). However, accumulating evidence suggests that type I and type II IFNs may not be restricted to independent pathways. Using different cell types deficient in IFNAR1, IFNAR2, IFNGR1, IFNGR2 and IFN-γ, we evaluated the contribution of each element of the IFN system to the activity of type I and type II IFNs. We show that deficiency in IFNAR1 or IFNAR2 is associated with impairment of type II IFN activity. This impairment, presumably resulting from the disruption of the ligand-receptor complex, is obtained in all cell types tested. However, deficiency of IFNGR1, IFNGR2 or IFN-γ was associated with an impairment of type I IFN activity in spleen cells only, correlating with the constitutive expression of type II IFN (IFN-γ) observed on those cells. Therefore, in vitro the constitutive expression of both the receptors and the ligands of type I or type II IFN is critical for the enhancement of the IFN activity. Any IFN deficiency can totally or partially impair IFN activity, suggesting the importance of type I and type II IFN interactions. Taken together, our results suggest that type I and type II IFNs may regulate biological activities through distinct as well as common IFN receptor complexes.
authors.affiliation: Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, Piscataway, NJ, USA; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Lasfar
authors.forename: Jeffry R
authors.initials: JR
authors.lastname: Cook
authors.forename: Karine A
authors.initials: KA
authors.lastname: Cohen Solal
authors.forename: Kenneth
authors.initials: K
authors.lastname: Reuhl
authors.forename: Sergei V
authors.initials: SV
authors.lastname: Kotenko
authors.forename: Jerome A
authors.initials: JA
authors.lastname: Langer
authors.forename: Debra L
authors.initials: DL
authors.lastname: Laskin
mesh_terms: D000818:Animals; D007370:Interferon Type I / Q000276:immunology* / Q000378:metabolism*; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*
chemical_list: C508032:Ifnar1 protein, mouse; C508034:Ifnar2 protein, mouse; D007370:Interferon Type I; D008024:Ligands; D053633:Receptor, Interferon alpha-beta; D007371:Interferon-gamma
keywords: T cells; cell types; constitutive interferon; interferon receptor paradigm; interferon response; type I and type II interferon receptors