Macrophage-derived reactive oxygen species protects against autoimmune priming with a defined polymeric adjuvant

Akhilesh Kumar Shakya, Ashok Kumar, Rikard Holmdahl, Kutty Selva Nandakumar

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Understanding the nature of adjuvants and the immune priming events in autoimmune diseases, such as rheumatoid arthritis, is a key challenge to identify their aetiology. Adjuvants are, however, complex structures with inflammatory and immune priming properties. Synthetic polymers provide a possibility to separate these functions and allow studies of the priming mechanisms in vivo. A well-balanced polymer, poly-N-isopropyl acrylamide (PNiPAAm) mixed with collagen type II (CII) induced relatively stronger autoimmunity and arthritis compared with more hydrophilic (polyacrylamide) or hydrophobic (poly-N-isopropylacrylamide-co-poly-N-tertbutylacrylamide and poly-N-tertbutylacrylamide) polymers. Clearly, all the synthesized polymers except the more hydrophobic poly-N-tertbutylacrylamide induced arthritis, especially in Ncf1-deficient mice, which are deficient in reactive oxygen species (ROS) production. We identified macrophages as the major infiltrating cells present at PNiPAAm-CII injection sites and demonstrate that ROS produced by the macrophages attenuated the immune response and the development of arthritis. Our results reveal that thermo-responsive polymers with high immune priming capacity could trigger an autoimmune response to CII and the subsequent arthritis development, in particular in the absence of NOX2 derived ROS. Importantly, ROS from macrophages protected against the autoimmune priming, demonstrating a critical regulatory role of macrophages in immune priming events.

Original languageEnglish
Pages (from-to)125-132
Number of pages8
JournalImmunology
Volume147
Issue number1
DOIs
StatePublished - Jan 1 2016

Keywords

  • Adjuvant
  • Arthritis
  • Collagen type II
  • Macrophages
  • Poly-N-isopropylacrylamide

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