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Definition of IFN-g...
Definition of IFN-gamma-related pathways critical for chemically-induced systemic autoimmunity
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- Pollard, Michael K (författare)
- Scripps Research Institute, USA
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- Hultman, Per (författare)
- Östergötlands Läns Landsting,Linköpings universitet,Molekylär och immunologisk patologi,Hälsouniversitetet,Klinisk patologi och klinisk genetik
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- Toomey, Christopher B. (författare)
- Scripps Research Institute, USA
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- Cauvi, David M. (författare)
- Scripps Research Institute, USA
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- Hoffman, Hal M. (författare)
- University of Calif San Diego, USA
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- Hamel, John C. (författare)
- Scripps Research Institute, USA
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- Kono, Dwight H. (författare)
- Scripps Research Institute, USA
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(creator_code:org_t)
- Elsevier, 2012
- 2012
- Engelska.
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Ingår i: Journal of Autoimmunity. - : Elsevier. - 0896-8411 .- 1095-9157. ; 39:4, s. 323-331
- Relaterad länk:
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https://europepmc.or...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Nyckelord
- Interferon
- Animal model
- Mercury
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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