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Macrophages suppres...
Macrophages suppress T cell responses and arthritis development in mice by producing reactive oxygen species
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- Gelderman, Kyra (författare)
- Lund University,Lunds universitet,Immunologi,Forskargrupper vid Lunds universitet,Immunology,Lund University Research Groups,Lund University, Lund, Sweden
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- Hultqvist, Malin (författare)
- Lund University,Lunds universitet,Immunologi,Forskargrupper vid Lunds universitet,Immunology,Lund University Research Groups,Lund University, Lund, Sweden
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- Pizzolla, Angela (författare)
- Lund University,Lunds universitet,Immunologi,Forskargrupper vid Lunds universitet,Immunology,Lund University Research Groups,Lund University, Lund, Sweden
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- Zhao, Ming (författare)
- Lund University,Lunds universitet,Kardiovaskulär forskning - immunitet och ateroskleros,Forskargrupper vid Lunds universitet,Cardiovascular Research - Immunity and Atherosclerosis,Lund University Research Groups,Lund University, Lund, Sweden
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- Nandakumar, Kutty Selva, 1965- (författare)
- Lund University,Lunds universitet,Immunologi,Forskargrupper vid Lunds universitet,Immunology,Lund University Research Groups,Lund University, Lund, Sweden
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- Mattsson, Ragnar (författare)
- Lund University,Lunds universitet,Immunologi,Forskargrupper vid Lunds universitet,Immunology,Lund University Research Groups,Lund University, Lund, Sweden
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- Holmdahl, Rikard (författare)
- Lund University,Lunds universitet,Immunologi,Forskargrupper vid Lunds universitet,Immunology,Lund University Research Groups,Lund University, Lund, Sweden; Turku University, Turku, Finland
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(creator_code:org_t)
- 2007
- 2007
- Engelska.
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Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 117:10, s. 3020-3028
- Relaterad länk:
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https://doi.org/10.1...
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http://dx.doi.org/10...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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Abstract
Ämnesord
Stäng
- Reduced capacity to produce ROS increases the severity of T cell-dependent arthritis in both mice and rats with polymorphisms in neutrophil cytosolic factor 1 (Ncf1) (p47phox). Since T cells cannot exert oxidative burst, we hypothesized that T cell responsiveness is downregulated by ROS produced by APCs. Macrophages have the highest burst capacity among APCs, so to study the effect of macrophage ROS on T cell activation, we developed transgenic mice expressing functional Ncf1 restricted to macrophages. Macrophage-restricted expression of functional Ncf1 restored arthritis resistance to the level of that of wild-type mice in a collagen-induced arthritis model but not in a T cell-independent anti-collagen antibody-induced arthritis model. T cell activation was downregulated and skewed toward Th2 in transgenic mice. In vitro, IL-2 production and T cell proliferation were suppressed by macrophage ROS, irrespective of T cell origin. IFN-gamma production, however, was independent of macrophage ROS but dependent on T cell origin. These effects were antigen dependent but not restricted to collagen type II. In conclusion, macrophage-derived ROS play a role in T cell selection, maturation, and differentiation, and also a suppressive role in T cell activation, and thereby mediate protection against autoimmune diseases like arthritis.
Ämnesord
- 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)
Nyckelord
- Animals
- Antigen-Presenting Cells/immunology
- Antigens/immunology
- Arthritis/*immunology
- *Autoimmunity
- Collagen Type II/immunology
- Genotype
- Interferon-gamma/metabolism
- Interleukin-2/metabolism
- Lymphocyte Activation
- Macrophages/*immunology
- Mice
- Mice
- Transgenic
- Mutation
- NADPH Oxidases/genetics/metabolism
- Reactive Oxygen Species/*metabolism
- Th1 Cells/*immunology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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