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Cutting Edge :
Cutting Edge : Processing of Oxidized Peptides in Macrophages Regulates T Cell Activation and Development of Autoimmune Arthritis
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- Yang, Min (author)
- Karolinska Institutet
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- Haase, Claus (author)
- Novo Nordisk AS, Global Res, DK-2880 Bagsvaerd, Denmark.
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- Viljanen, Johan V. (author)
- Uppsala universitet,Organisk kemi
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- Xu, Bingze (author)
- Karolinska Institutet
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- Ge, Changrong (author)
- Karolinska Institutet
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- Kihlberg, Jan (author)
- Uppsala universitet,Organisk kemi
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- Holmdahl, Rikard (author)
- Karolinska Institutet
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Karolinska Institutet Novo Nordisk AS, Global Res, DK-2880 Bagsvaerd, Denmark (creator_code:org_t)
- 2017-12-15
- 2017
- English.
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In: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 199:12, s. 3937-3942
- Related links:
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https://www.jimmunol...
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https://urn.kb.se/re...
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https://doi.org/10.4...
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http://kipublication...
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Abstract
Subject headings
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- APCs are known to produce NADPH oxidase (NOX) 2-derived reactive oxygen species; however, whether and how NOX2-mediated oxidation affects redox-sensitive immunogenic peptides remains elusive. In this study, we investigated a major immunogenic peptide in glucose-6-phosphate isomerase (G6PI), a potential autoantigen in rheumatoid arthritis, which can form internal disulfide bonds. Ag presentation assays showed that presentation of this G6PI peptide was more efficient in NOX2-deficient (Ncf1(m1J/m1J) mutant) mice, compared with wild-type controls. IFN-gamma-inducible lysosomal thiol reductase (GILT), which facilitates disulfide bond-containing Ag processing, was found to be upregulated in macrophages from Ncf1 mutant mice. Ncf1 mutant mice exhibited more severe G6PI peptide-induced arthritis, which was accompanied by the increased GILT expression in macrophages and enhanced Ag-specific T cell responses. Our results show that NOX2-dependent processing of the redox-sensitive autoantigens by APCs modify T cell activity and development of autoimmune arthritis.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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