Definition of IFN-gamma-related pathways critical for chemically-induced systemic autoimmunity
2012 (English)In: Journal of Autoimmunity, ISSN 0896-8411, E-ISSN 1095-9157, Vol. 39, no 4, 323-331 p.Article in journal (Refereed) Published
IFN-gamma is essential for idiopathic and murine mercury-induced systemic autoimmunity (mHgIA), and heterozygous IFN-gamma(+/-) mice also exhibit reduced disease. This suggests that blocking specific IFN-gamma-related pathways that may only partially inhibit IFN-gamma production or function will also suppress autoimmunity. To test this hypothesis, mice deficient in genes regulating IFN-gamma 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-gamma 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-gamma expression in contrast to those that mediate later signaling events. These findings have implications for the therapeutic targeting of IFN-gamma pathways in systemic autoimmunity.
Place, publisher, year, edition, pages
Elsevier , 2012. Vol. 39, no 4, 323-331 p.
Interferon, Animal model, Mercury
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-88671DOI: 10.1016/j.jaut.2012.04.003ISI: 000313465800009OAI: oai:DiVA.org:liu-88671DiVA: diva2:605479
Funding Agencies|NIH|ES007511ES014847AI052430AR053731|Swedish Research Council Branch of Medicine|09453|2013-02-142013-02-142013-02-14