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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2017,11,21]]},"abstract":"<jats:p>\n                    The circadian system regulates numerous physiological processes including immune responses. Here, we show that mice deficient of the circadian clock genes\n                    <jats:italic>Cry1<\/jats:italic>\n                    and\n                    <jats:italic>Cry2<\/jats:italic>\n                    [\n                    <jats:italic>Cry<\/jats:italic>\n                    double knockout (DKO)] develop an autoimmune phenotype including high serum IgG concentrations, serum antinuclear antibodies, and precipitation of IgG, IgM, and complement 3 in glomeruli and massive infiltration of leukocytes into the lungs and kidneys. Flow cytometry of lymphoid organs revealed decreased pre-B cell numbers and a higher percentage of mature recirculating B cells in the bone marrow, as well as increased numbers of B2 B cells in the peritoneal cavity of\n                    <jats:italic>Cry<\/jats:italic>\n                    DKO mice. The B cell receptor (BCR) proximal signaling pathway plays a critical role in autoimmunity regulation. Activation of\n                    <jats:italic>Cry<\/jats:italic>\n                    DKO splenic B cells elicited markedly enhanced tyrosine phosphorylation of cellular proteins compared with cells from control mice, suggesting that overactivation of the BCR-signaling pathway may contribute to the autoimmunity phenotype in the\n                    <jats:italic>Cry<\/jats:italic>\n                    DKO mice. In addition, the expression of\n                    <jats:italic>C1q<\/jats:italic>\n                    , the deficiency of which contributes to the pathogenesis of systemic lupus erythematosus, was significantly down-regulated in\n                    <jats:italic>Cry<\/jats:italic>\n                    DKO B cells. Our results suggest that B cell development, the BCR-signaling pathway, and\n                    <jats:italic>C1q<\/jats:italic>\n                    expression are regulated by circadian clock CRY proteins and that their dysregulation through loss of CRY contributes to autoimmunity.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1619119114","type":"journal-article","created":{"date-parts":[[2017,11,6]],"date-time":"2017-11-06T15:21:35Z","timestamp":1509981695000},"page":"12548-12553","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":101,"title":["Circadian clock cryptochrome proteins regulate autoimmunity"],"prefix":"10.1073","volume":"114","author":[{"given":"Qi","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Hematology and Oncology, Cedars-Sinai Medical Center, Los Angeles, CA 90048;"},{"name":"Department of Pathology and Laboratory Medicine, LAC+USC Medical Center, Los Angeles, CA 90033;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Cedars-Sinai Medical Center, Los Angeles, CA 90048;"},{"name":"Xiang An Hospital of Xiamen University","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigal","family":"Gery","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Cedars-Sinai Medical Center, Los Angeles, CA 90048;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Cedars-Sinai Medical Center, Los Angeles, CA 90048;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De-Chen","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Cedars-Sinai Medical Center, Los Angeles, CA 90048;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Cedars-Sinai Medical Center, Los Angeles, CA 90048;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengshan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, LAC+USC Medical Center, Los Angeles, CA 90033;"},{"name":"Department of Systems Biology, Beckman Research Institute, City of Hope National Medical Center, Pasadena, CA 91016;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Mack","sequence":"additional","affiliation":[{"name":"Nomis Foundation Laboratories for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, La Jolla, CA 92037;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Yang","sequence":"additional","affiliation":[{"name":"National University of Singapore","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruishu","family":"Deng","sequence":"additional","affiliation":[{"name":"Sanford Burnham Preybs Medical Discovery Institute, La Jolla, CA 92037;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianping","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Cedars-Sinai Medical Center, Los Angeles, CA 90048;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling-Wa","family":"Chong","sequence":"additional","affiliation":[{"name":"Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Cho","sequence":"additional","affiliation":[{"name":"Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjun","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Cedars-Sinai Medical Center, Los Angeles, CA 90048;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan-Zhen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Immunology, Microarray Core Facility, University of Texas Southwestern Medical Center, Dallas, TX 75390;"},{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"M\u00fcschen","sequence":"additional","affiliation":[{"name":"Department of Systems 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