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 CD44hi and CD44hiCD55lo 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.
Original language | English (US) |
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Pages (from-to) | 323-331 |
Number of pages | 9 |
Journal | Journal of Autoimmunity |
Volume | 39 |
Issue number | 4 |
DOIs | |
State | Published - Dec 2012 |
Externally published | Yes |
Keywords
- Animal model
- Interferon
- Mercury
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology