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Obesity is considered a chronic disease with a connection with autoimmune diseases through systemic inflammation. However, an obesity and autoimmune disease connection is not consistently true in rodent models of autoimmune disease. A mouse model of human autoimmune uveitis, experimental autoimmune uveitis (EAU) has been used to better understand the immunobiology of uveitis. In this study, we assessed EAU in a high-fat diet (HFD) obesity model and found that the EAU severity is significantly higher in wild-type mice, but not in HFD melanocortin 5 receptor deficient mice. We find a decrease in CD11b+F4\/80+Ly-6CloLy-6G+ M\u03d5s, previously shown to be suppressive, and an enhancement of a Th1 response at the onset of EAU in obese mice. We further demonstrate that at recovery of EAU, obese mice lack regulatory immunity that provides protection from EAU. This report demonstrates that obesity exacerbates autoimmune uveitis and inhibits the promotion of post-EAU regulatory immunity through the melanocortin 5 receptor. The implication of this work is that obesity may contribute to the prevalence of autoimmune uveitis.<\/jats:p>","DOI":"10.1002\/jlb.ma0119-030rr","type":"journal-article","created":{"date-parts":[[2019,7,9]],"date-time":"2019-07-09T14:40:52Z","timestamp":1562683252000},"page":"879-887","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Exacerbation of autoimmune uveitis by obesity occurs through the melanocortin 5 receptor"],"prefix":"10.1093","volume":"106","author":[{"given":"Fauziyya Y","family":"Muhammad","sequence":"first","affiliation":[{"name":"Department of Ophthalmology\/Dean McGee Eye Institute, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma, USA"}]},{"given":"Kayleigh","family":"Peters","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology\/Dean McGee Eye Institute, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma, USA"}]},{"given":"Dawei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology\/Dean McGee Eye Institute, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0036-9620","authenticated-orcid":false,"given":"Darren J","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology\/Dean McGee Eye Institute, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma, USA"}]}],"member":"286","published-online":{"date-parts":[[2019,7,9]]},"reference":[{"key":"2023032500061287500_jlb10455-cit-0001","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1056\/NEJMoa1614362","article-title":"Health effects of overweight and obesity in 195 countries over 25 years","volume":"377","author":"Collaborators GBDO","year":"2017","journal-title":"N Engl J Med"},{"key":"2023032500061287500_jlb10455-cit-0002","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/oby.22378","article-title":"Obesity as a disease: the Obesity Society 2018 position statement","volume":"27","author":"Jastreboff","year":"2019","journal-title":"Obesity"},{"key":"2023032500061287500_jlb10455-cit-0003","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.ecl.2016.04.004","article-title":"Regarding obesity as a disease: evolving policies and their implications","volume":"45","author":"Kyle","year":"2016","journal-title":"Endocrinol Metab Clin North Am"},{"key":"2023032500061287500_jlb10455-cit-0004","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/S0140-6736(14)60460-8","article-title":"Global, regional, and national prevalence of overweight and obesity in children and adults during 1980\u20132013: a systematic analysis for the Global Burden of Disease Study 2013","volume":"384","author":"Ng","year":"2014","journal-title":"The Lancet"},{"key":"2023032500061287500_jlb10455-cit-0005","doi-asserted-by":"crossref","first-page":"598","DOI":"10.4239\/wjd.v6.i4.598","article-title":"Type 2 diabetes mellitus: from a metabolic disorder to an inflammatory condition","volume":"6","author":"Hameed","year":"2015","journal-title":"World J Diabetes"},{"key":"2023032500061287500_jlb10455-cit-0006","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1001\/archopht.1962.00960030506014","article-title":"Epidemiology of uveitis. 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