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In this study, we show that mAb blockade revealed a unique role for IFN-\u03b2 in Lyme arthritis development in B6.C3-Bbaa1 mice. Genetic control of IFN-\u03b2 expression was also identified in bone marrow\u2013derived macrophages stimulated with B. burgdorferi, and it was responsible for feed-forward amplification of IFN-stimulated genes. Reciprocal radiation chimeras between B6.C3-Bbaa1 and C57BL\/6 mice revealed that arthritis is initiated by radiation-sensitive cells, but orchestrated by radiation-resistant components of joint tissue. Advanced congenic lines were developed to reduce the physical size of the Bbaa1 interval, and confirmed the contribution of type I IFN genes to Lyme arthritis. RNA sequencing of resident CD45\u2212 joint cells from advanced interval-specific recombinant congenic lines identified myostatin as uniquely upregulated in association with Bbaa1 arthritis development, and myostatin expression was linked to IFN-\u03b2 production. Inhibition of myostatin in vivo suppressed Lyme arthritis in the reduced interval Bbaa1 congenic mice, formally implicating myostatin as a novel downstream mediator of the joint-specific inflammatory response to B. burgdorferi.<\/jats:p>","DOI":"10.4049\/jimmunol.1701011","type":"journal-article","created":{"date-parts":[[2017,10,7]],"date-time":"2017-10-07T00:25:44Z","timestamp":1507335944000},"page":"3525-3534","source":"Crossref","is-referenced-by-count":15,"title":["Genetic Control of Lyme Arthritis by <i>Borrelia burgdorferi<\/i> Arthritis\u2013Associated Locus 1 Is Dependent on Localized Differential Production of IFN-\u03b2 and Requires Upregulation of Myostatin"],"prefix":"10.1093","volume":"199","author":[{"given":"Jackie K","family":"Paquette","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Utah , Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Utah , Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3688-6283","authenticated-orcid":false,"given":"Colleen","family":"Fisher","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Utah , Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9108-6927","authenticated-orcid":false,"given":"Jinze","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Utah , Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9965-755X","authenticated-orcid":false,"given":"Sang Beum","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Human Nutrition, Food, and Animal Sciences, University of Hawaii at Manoa , Honolulu, HI 96822"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James F","family":"Zachary","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathobiology, University of Illinois at Urbana-Champaign , Urbana, IL 61820"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6648-8430","authenticated-orcid":false,"given":"Yong Soo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Human Nutrition, Food, and Animal Sciences, University of Hawaii at Manoa , Honolulu, HI 96822"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cory","family":"Teuscher","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Vermont , Burlington, VT 05405"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7214-5987","authenticated-orcid":false,"given":"Janis J","family":"Weis","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Utah , Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,11,15]]},"reference":[{"key":"2025030614521516200_r1","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1001\/jama.2013.278331","article-title":"CDC estimates 300,000 US cases of Lyme disease annually","volume":"310","author":"Kuehn","year":"2013","journal-title":"JAMA"},{"key":"2025030614521516200_r2","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.jneuroim.2012.10.011","article-title":"Increased IFN\u03b1 activity and differential antibody response in patients with a history of Lyme disease and persistent cognitive deficits","volume":"255","author":"Jacek","year":"2013","journal-title":"J. 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