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Macrophages suppress T cell responses and arthritis development in mice by producing reactive oxygen species

In English

Författare

  • Kyra Gelderman
  • Malin Hultqvist
  • Angela Pizzolla
  • Ming Zhao
  • Nandakumar Kutty Selva
  • Ragnar Mattsson
  • Rikard Holmdahl

Summary, in English

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.

Publiceringsår

2007

Språk

Engelska

Sidor

3020-3028

Publikation/Tidskrift/Serie

Journal of Clinical Investigation

Volym

117

Issue

10

Dokumenttyp

Artikel i tidskrift

Förlag

The American Society for Clinical Investigation

Ämne

  • Immunology in the medical area

Status

Published

Forskningsgrupp

  • Immunology
  • Cardiovascular Research - Immunity and Atherosclerosis

ISBN/ISSN/Övrigt

  • ISSN: 0021-9738