{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T05:55:32Z","timestamp":1788328532315,"version":"build-2803163510"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000},"content-version":"vor","delay-in-days":525,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Phospholipase D4 (PLD4) is an endolysosomal exonuclease of ssRNA and ssDNA, rather than a phospholipase as its name suggests. Human polymorphisms in the PLD4 gene have been linked by genome-wide association studies to systemic sclerosis, rheumatoid arthritis, and systemic lupus erythematosus. However, B6.129 Pld4\u2212\/\u2212 mice develop features of a distinct disease, macrophage activation syndrome, which is reversed in mice mutated in TLR9. In this article, we compare a Pld4 null mutant identified on the BALB\/c background, Pld4thss\/thss, which has distinct phenotypes: short stature, thin hair, and features of systemic lupus erythematosus. All phenotypes analyzed were largely normalized in Pld4thss\/thssTlr9\u2212\/\u2212 mice. Thus, Pld4thss\/thss represents a rare model in which mouse lupus etiology is TLR9 dependent. Compared with PLD4-deficient B6 mice, Pld4thss\/thss mice had elevated levels of serum IgG, IgG anti-dsDNA autoantibodies, BAFF, and IFN-\u03b3 and elevated B cell numbers. Overall, the data suggest that PLD4 deficiency can lead to a diverse array of rheumatological abnormalities depending upon background-modifying genes, and that these diseases of PLD4 deficiency are largely driven by TLR9 recognition of ssDNA.<\/jats:p>","DOI":"10.4049\/immunohorizons.2300058","type":"journal-article","created":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T14:01:00Z","timestamp":1691589660000},"page":"577-586","source":"Crossref","is-referenced-by-count":12,"title":["Disease in the <i>Pld4<\/i>thss\/thss Model of Murine Lupus Requires TLR9"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9921-4225","authenticated-orcid":false,"given":"Amanda L","family":"Gavin","sequence":"first","affiliation":[{"name":"Department of Immunology and Microbiology, The Scripps Research Institute , La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya R","family":"Blane","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Scripps Research Institute , La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Therese C","family":"Thinnes","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Scripps Research Institute , La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9720-1957","authenticated-orcid":false,"given":"Emma","family":"Gerlt","sequence":"additional","affiliation":[{"name":"University of California , Merced, Merced, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2136-8130","authenticated-orcid":false,"given":"Ann","family":"Marshak-Rothstein","sequence":"additional","affiliation":[{"name":"University of Massachusetts Medical School , Worcester, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deli","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Scripps Research Institute , La Jolla, CA"},{"name":"Life Sciences Institute, Zhejiang University , Hangzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4769-6311","authenticated-orcid":false,"given":"David","family":"Nemazee","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Scripps Research Institute , La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,8,9]]},"reference":[{"key":"2025010703563272500_r1","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/35056009","article-title":"Modifier genes in mice and humans","volume":"2","author":"Nadeau","year":"2001","journal-title":"Nat. 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