{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:27:53Z","timestamp":1787030873664,"version":"build-2736575974"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2017,10,1]],"date-time":"2017-10-01T00:00:00Z","timestamp":1506816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) display unique aggressive behavior, invading the articular cartilage and promoting inflammation. Using an integrative analysis of RA risk alleles, the transcriptome and methylome in RA FLS, we recently identified the limb bud and heart development (LBH) gene as a key dysregulated gene in RA and other autoimmune diseases. Although some evidence suggests that LBH could modulate the cell cycle, the precise mechanism is unknown and its impact on inflammation in vivo has not been defined. Our cell cycle analysis studies show that LBH deficiency in FLS leads to S-phase arrest and failure to progress through the cell cycle. LBH-deficient FLS had increased DNA damage and reduced expression of the catalytic subunit of DNA polymerase \u03b1. Decreased DNA polymerase \u03b1 was followed by checkpoint arrest due to phosphorylation of checkpoint kinase 1. Because DNA fragments can increase arthritis severity in preclinical models, we then explored the effect of LBH deficiency in the K\/BxN serum transfer model. Lbh knockout exacerbated disease severity, which is associated with elevated levels of IL-1\u03b2 and checkpoint kinase 1 phosphorylation. These studies indicate that LBH deficiency induces S-phase arrest that, in turn, exacerbates inflammation. Because LBH gene variants are associated with type I diabetes mellitus, systemic lupus erythematosus, RA, and celiac disease, these results suggest a general mechanism that could contribute to immune-mediated diseases.<\/jats:p>","DOI":"10.4049\/jimmunol.1700719","type":"journal-article","created":{"date-parts":[[2017,8,14]],"date-time":"2017-08-14T20:30:20Z","timestamp":1502742620000},"page":"2316-2322","source":"Crossref","is-referenced-by-count":25,"title":["Regulation of the Cell Cycle and Inflammatory Arthritis by the Transcription Cofactor\n                    <i>LBH<\/i>\n                    Gene"],"prefix":"10.1093","volume":"199","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8711-7321","authenticated-orcid":false,"given":"Shinji","family":"Matsuda","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Allergy and Immunology, University of California San Diego School of Medicine , La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepa","family":"Hammaker","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy and Immunology, University of California San Diego School of Medicine , La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6713-4308","authenticated-orcid":false,"given":"Katharyn","family":"Topolewski","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy and Immunology, University of California San Diego School of Medicine , La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karoline J","family":"Briegel","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Miami Miller School of Medicine , Miami, FL 33136"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L","family":"Boyle","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy and Immunology, University of California San Diego School of Medicine , La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Dowdy","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, University of California San Diego School of Medicine , La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of California San Diego School of Medicine , La Jolla, CA 92093"},{"name":"Department of Cellular and Molecular Medicine, University of California San Diego School of Medicine , La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary S","family":"Firestein","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy and Immunology, University of California San Diego School of Medicine , La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,10,1]]},"reference":[{"key":"2025030614470381500_r1","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/nrrheum.2012.232","article-title":"Rheumatoid arthritis in 2012: progress in RA genetics, pathology and therapy","volume":"9","author":"van Vollenhoven","year":"2013","journal-title":"Nat. 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