Definition of IFN-γ-related pathways critical for chemically-induced systemic autoimmunity.

Journal of Autoimmunity
K Michael PollardDwight H Kono

Abstract

IFN-γ is essential for idiopathic and murine mercury-induced systemic autoimmunity (mHgIA), and heterozygous IFN-γ(+/-) mice also exhibit reduced disease. This suggests that blocking specific IFN-γ-related pathways that may only partially inhibit IFN-γ production or function will also suppress autoimmunity. To test this hypothesis, mice deficient in genes regulating IFN-γ expression (Casp1, Nlrp3, Il12a, Il12b, Stat4) or function (Ifngr1, Irf1) were examined for mHgIA susceptibility. Absence of either Ifngr1 or Irf1 resulted in a striking reduction of disease, while deficiency of genes promoting IFN-γ expression had modest to no effect. Furthermore, both Irf1- and Ifng-deficiency only modestly reduced the expansion of CD44(hi) and CD44(hi)CD55(lo) CD4(+) T cells, indicating that they are not absolutely required for T cell activation. Thus, there is substantial redundancy in genes that regulate IFN-γ expression in contrast to those that mediate later signaling events. These findings have implications for the therapeutic targeting of IFN-γ pathways in systemic autoimmunity.

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Citations

Aug 27, 2013·Clinical Reviews in Allergy & Immunology·Carlo Selmi
Apr 6, 2013·BMC Medicine·Kenneth Michael Pollard, Dwight H Kono
Sep 23, 2014·Toxicological Sciences : an Official Journal of the Society of Toxicology·Christopher B ToomeyK Michael Pollard
Mar 26, 2016·Frontiers in Immunology·Kenneth Michael Pollard
Apr 24, 2014·Arthritis & Rheumatology·J Michelle Kahlenberg, Mariana J Kaplan
Nov 13, 2013·Autoimmunity·Inez RogatskyAlessandra B Pernis
Sep 28, 2016·International Immunopharmacology·Xiao LiuJinhua Xu
Apr 30, 2017·Toxicological Sciences : an Official Journal of the Society of Toxicology·David M CauviKenneth Michael Pollard
Mar 15, 2015·Toxicology and Industrial Health·Alla S ArefievaMarina S Krasilshchikova
Oct 22, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·K Michael PollardDwight H Kono
Feb 13, 2018·Journal of Behavioral Medicine·R I FalkenbergM L Peters
May 15, 2018·Frontiers in Immunology·Jessica M MayeuxKenneth M Pollard
Nov 8, 2018·International Journal of Molecular Sciences·Dorota FormanowiczPiotr Formanowicz
Dec 16, 2020·Environmental Pollution·Jahnavi SharmaPradyumna Kumar Mishra

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