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Definition of IFN-gamma-related pathways critical for chemically-induced systemic autoimmunity
Scripps Research Institute, USA .
Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
Scripps Research Institute, USA .
Scripps Research Institute, USA .
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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
Abstract [en]

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.
Keyword [en]
Interferon, Animal model, Mercury
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-88671DOI: 10.1016/j.jaut.2012.04.003ISI: 000313465800009OAI: diva2:605479

Funding Agencies|NIH|ES007511ES014847AI052430AR053731|Swedish Research Council Branch of Medicine|09453|

Available from: 2013-02-14 Created: 2013-02-14 Last updated: 2013-02-14

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Hultman, Per
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Molecular and Immunological PathologyFaculty of Health SciencesDepartment of Clinical Pathology and Clinical Genetics
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