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Nonobese diabetic (NOD) mice spontaneously develop inflammation of lacrimal and salivary glands with histopathological features similar to SS in humans including focal lymphocytic infiltrates in the affected glands. The innate immune signals driving lymphocytic infiltration of these glands are not well-defined. Here we evaluate the role of Toll-like receptor (TLR) 7 in the development of SS-like manifestations in NOD mice. We created a Tlr7 knockout NOD mouse strain and performed histological and gene expression studies to characterize the effects of TLR7 on autoimmunity development. TLR7 was required for male-specific lacrimal gland inflammation but not for female-specific salivary gland inflammation. Moreover, TLR7 was required for type 1 diabetes development in male but not female NOD mice. RNA sequencing demonstrated that TLR7 was associated with a type I interferon (IFN) response and a type I IFN-independent B cell response in the lacrimal glands. Together these studies identify a previously unappreciated pathogenic role for TLR7 in lacrimal gland autoimmunity and T1D development in male NOD mice adding to the growing body of evidence supporting sex differences in mechanisms of autoimmune disease in NOD mice.<\/jats:p>","DOI":"10.3390\/ijms21249478","type":"journal-article","created":{"date-parts":[[2020,12,13]],"date-time":"2020-12-13T23:39:36Z","timestamp":1607902776000},"page":"9478","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Toll-Like Receptor 7 Is Required for Lacrimal Gland Autoimmunity and Type 1 Diabetes Development in Male Nonobese Diabetic Mice"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9894-1391","authenticated-orcid":false,"given":"Ivy L.","family":"Debreceni","sequence":"first","affiliation":[{"name":"Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA"},{"name":"Immunology Graduate Program, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael S.","family":"Chimenti","sequence":"additional","affiliation":[{"name":"Iowa Institute of Human Genetics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7614-5925","authenticated-orcid":false,"given":"David V.","family":"Serreze","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME 04609, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aron M.","family":"Geurts","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Guang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Max McGee National Research Center for Juvenile Diabetes, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4082-7582","authenticated-orcid":false,"given":"Scott M.","family":"Lieberman","sequence":"additional","affiliation":[{"name":"Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA"},{"name":"Immunology Graduate Program, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.clim.2019.04.009","article-title":"Sjogren\u2019s syndrome: An update on disease pathogenesis, clinical manifestations and treatment","volume":"203","author":"Vivino","year":"2019","journal-title":"Clin. 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