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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 <jats:italic>in vivo<\/jats:italic>. A well\u2010balanced polymer, poly\u2010<jats:italic>N<\/jats:italic>\u2010isopropyl acrylamide (<jats:styled-content style=\"fixed-case\">PN<\/jats:styled-content>i<jats:styled-content style=\"fixed-case\">PAA<\/jats:styled-content>m) mixed with collagen type <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">CII<\/jats:styled-content>) induced relatively stronger autoimmunity and arthritis compared with more hydrophilic (polyacrylamide) or hydrophobic (poly\u2010<jats:italic>N<\/jats:italic>\u2010isopropylacrylamide\u2010<jats:italic>co<\/jats:italic>\u2010poly\u2010<jats:italic>N<\/jats:italic>\u2010tertbutylacrylamide and poly\u2010<jats:italic>N<\/jats:italic>\u2010tertbutylacrylamide) polymers. Clearly, all the synthesized polymers except the more hydrophobic poly\u2010<jats:italic>N<\/jats:italic>\u2010tertbutylacrylamide induced arthritis, especially in <jats:italic>Ncf1<\/jats:italic>\u2010deficient mice, which are deficient in reactive oxygen species (<jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content>) production. We identified macrophages as the major infiltrating cells present at <jats:styled-content style=\"fixed-case\">PN<\/jats:styled-content>i<jats:styled-content style=\"fixed-case\">PAA<\/jats:styled-content>m\u2010<jats:styled-content style=\"fixed-case\">CII<\/jats:styled-content> injection sites and demonstrate that <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content> produced by the macrophages attenuated the immune response and the development of arthritis. Our results reveal that thermo\u2010responsive polymers with high immune priming capacity could trigger an autoimmune response to <jats:styled-content style=\"fixed-case\">CII<\/jats:styled-content> and the subsequent arthritis development, in particular in the absence of <jats:styled-content style=\"fixed-case\">NOX<\/jats:styled-content>2 derived <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content>. Importantly, <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content> from macrophages protected against the autoimmune priming, demonstrating a critical regulatory role of macrophages in immune priming events.<\/jats:p>","DOI":"10.1111\/imm.12546","type":"journal-article","created":{"date-parts":[[2015,10,12]],"date-time":"2015-10-12T22:42:06Z","timestamp":1444689726000},"page":"125-132","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Macrophage\u2010derived reactive oxygen species protects against autoimmune priming with a defined polymeric adjuvant"],"prefix":"10.1111","volume":"147","author":[{"given":"Akhilesh Kumar","family":"Shakya","sequence":"first","affiliation":[{"name":"Medical Inflammation Research Department of Biochemistry and Biophysics Karolinska Institute Stockholm Sweden"},{"name":"Department of Chemical Engineering Texas Tech University Lubbock TX 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