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Infection of B6 IL-10 reporter mice identified macrophages and CD4+ T cells as the primary sources of IL-10 in the infected joint tissue, suggesting that early local production of IL-10 dampened the proarthritic IFN response. Treatment of B6 IL-10\u2212\/\u2212 mice with anti\u2013IFN-\u03b3 reduced the increase in arthritis severity and suppressed IFN-inducible transcripts to wild-type levels, thereby linking dysregulation of IFN-\u03b3 to disease in the B6 IL-10\u2212\/\u2212 mouse. Arthritis in B6 IL-10\u2212\/\u2212 mice was associated with elevated numbers of NK cell, NKT cell, \u03b1\/\u03b2 T cell, and macrophage infiltration of the infected joint. FACS lineage sorting revealed NK cells and CD4+ T cells as sources of IFN-\u03b3 in the joint tissue of B6 IL-10\u2212\/\u2212 mice. These findings suggest the presence of a positive-feedback loop in the joint tissue of infected B6 IL-10\u2212\/\u2212 mice, in which production of inflammatory chemokines, infiltration of IFN-\u03b3\u2013producing cells, and additional production of inflammatory cytokines result in arthritis. This mechanism of arthritis is in contrast to that seen in C3H\/He mice, in which arthritis development is linked to transient production of type I IFN and develops independently of IFN-\u03b3. Due to the sustained IFN response driven by NK cells and T cells, we propose the B6 IL-10\u2212\/\u2212 mouse as a potential model to study the persistent arthritis observed in some human Lyme disease patients.<\/jats:p>","DOI":"10.4049\/jimmunol.1102359","type":"journal-article","created":{"date-parts":[[2011,12,17]],"date-time":"2011-12-17T01:43:18Z","timestamp":1324086198000},"page":"1381-1393","source":"Crossref","is-referenced-by-count":53,"title":["Localized Production of IL-10 Suppresses Early Inflammatory Cell Infiltration and Subsequent Development of IFN-\u03b3\u2013Mediated Lyme Arthritis"],"prefix":"10.1093","volume":"188","author":[{"given":"F Lynn","family":"Sonderegger","sequence":"first","affiliation":[{"name":"Division of Microbiology and Immunology, Department of Pathology, University of Utah , Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Ma","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Department of Pathology, University of Utah , Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Maylor-Hagan","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Department of Pathology, University of Utah , Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Brewster","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Department of Pathology, University of Utah , Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaosong","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Department of Pathology, University of Utah , Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald J","family":"Spangrude","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Department of Pathology, University of Utah , Salt Lake City, UT 84112"},{"name":"Division of Hematology, Department of Medicine, University of Utah , Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James F","family":"Zachary","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, University of Illinois at Urbana-Champaign , Urbana, IL 61802"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H","family":"Weis","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Department of Pathology, University of Utah , Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janis J","family":"Weis","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Department of Pathology, University of Utah , Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,2,1]]},"reference":[{"key":"2025032409485080100_r1","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1172\/JCI21681","article-title":"The emergence of Lyme disease","volume":"113","author":"Steere","year":"2004","journal-title":"J. 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