{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T03:49:06Z","timestamp":1790480946121,"version":"4.1.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2008,10,1]],"date-time":"2008-10-01T00:00:00Z","timestamp":1222819200000},"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":[[2008,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>IL-23 stimulates the differentiation and function of the Th17 subset of CD4+ T cells and plays a critical role in chronic inflammation. The IL-23 receptor-encoding gene is also an inflammatory disease susceptibility gene. IL-23 shares a common subunit with IL-12, a T cell-dependent osteoclast formation inhibitor, and we found that IL-23 also dose-dependently inhibited osteoclastogenesis in a CD4+ T lymphocyte-dependent manner. When sufficiently enriched, \u03b3\u03b4 T cells also mediated IL-23 inhibition. Like IL-12, IL-23 acted synergistically with IL-18 to block osteoclastogenesis but, unlike IL-12, IL-23 action depended on T cell GM-CSF production. IL-23 did not mediate IL-12 action although IL-12 induced its expression. Male mice lacking IL-23 (IL-23p19\u2212\/\u2212) had \u223c30% lower bone mineral density and tibial trabecular bone mass (bone volume (BV)\/total volume (TV)) than wild-type littermates at 12 wk and 40% lower BV\/TV at 26 wk of age; male heterozygotes also had lower bone mass. Female IL-23p19\u2212\/\u2212 mice also had reduced BV\/TV. IL-23p19\u2212\/\u2212 mice had no detectable osteoclast defect in trabecular bone but IL-23p19\u2212\/\u2212 had thinner growth plate hypertrophic and primary spongiosa zones (and, in females, less cartilage remnants) compared with wild type. This suggests increased osteoclast action at and below the growth plate, leading to reduced amounts of mature trabecular bone. Thus, IL-23 inhibits osteoclast formation indirectly via T cells in vitro. Under nonpathological conditions (unlike inflammatory conditions), IL-23 favors higher bone mass in long bones by limiting resorption of immature bone forming below the growth plate.<\/jats:p>","DOI":"10.4049\/jimmunol.181.8.5720","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:47:01Z","timestamp":1397850421000},"page":"5720-5729","source":"Crossref","is-referenced-by-count":86,"title":["IL-23 Inhibits Osteoclastogenesis Indirectly through Lymphocytes and Is Required for the Maintenance of Bone Mass in Mice"],"prefix":"10.1093","volume":"181","author":[{"given":"Julian M W","family":"Quinn","sequence":"first","affiliation":[{"name":"St Vincent\u2019s Institute , Fitzroy, Victoria,","place":["Australia"]},{"name":"Department of Medicine, University of Melbourne, St. Vincent\u2019s Hospital , Fitzroy, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie A","family":"Sims","sequence":"additional","affiliation":[{"name":"St Vincent\u2019s Institute , Fitzroy, Victoria,","place":["Australia"]},{"name":"Department of Medicine, University of Melbourne, St. Vincent\u2019s Hospital , Fitzroy, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasnawati","family":"Saleh","sequence":"additional","affiliation":[{"name":"St Vincent\u2019s Institute , Fitzroy, Victoria,","place":["Australia"]},{"name":"Department of Medicine, University of Melbourne, St. Vincent\u2019s Hospital , Fitzroy, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danijela","family":"Mirosa","sequence":"additional","affiliation":[{"name":"St Vincent\u2019s Institute , Fitzroy, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Thompson","sequence":"additional","affiliation":[{"name":"St Vincent\u2019s Institute , Fitzroy, Victoria,","place":["Australia"]},{"name":"Institute of Medical Sciences, University of Aberdeen , Aberdeen,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stelios","family":"Bouralexis","sequence":"additional","affiliation":[{"name":"St Vincent\u2019s Institute , Fitzroy, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma C","family":"Walker","sequence":"additional","affiliation":[{"name":"St Vincent\u2019s Institute , Fitzroy, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T John","family":"Martin","sequence":"additional","affiliation":[{"name":"St Vincent\u2019s Institute , Fitzroy, Victoria,","place":["Australia"]},{"name":"Department of Medicine, University of Melbourne, St. Vincent\u2019s Hospital , Fitzroy, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew T","family":"Gillespie","sequence":"additional","affiliation":[{"name":"St Vincent\u2019s Institute , Fitzroy, Victoria,","place":["Australia"]},{"name":"Department of Medicine, University of Melbourne, St. Vincent\u2019s Hospital , Fitzroy, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,10,15]]},"reference":[{"key":"2026012807134391700_R1","first-page":"103","article-title":"Impact of cytokines and T lymphocytes upon osteoclast differentiation and function","volume-title":"Arthritis Res. Ther.","year":"2007"},{"key":"2026012807134391700_R2","first-page":"33","article-title":"Osteoimmunology: interplay between the immune system and bone metabolism","volume-title":"Annu. Rev. Immunol.","year":"2006"},{"key":"2026012807134391700_R3","first-page":"442","article-title":"The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene","volume-title":"Nature","year":"1990"},{"key":"2026012807134391700_R4","first-page":"3597","article-title":"Osteoclast differentiation factor is a ligand for osteoprotegerin\/osteoclastogenesis-inhibitory factor and is identical to TRANCE\/RANKL","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1998"},{"key":"2026012807134391700_R5","first-page":"315","article-title":"OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis","volume-title":"Nature","year":"1999"},{"key":"2026012807134391700_R6","first-page":"2075","article-title":"TRANCE (tumor necrosis factor [TNF]-related activation-induced cytokine), a new TNF family member predominantly expressed in T cells, is a dendritic cell-specific survival factor","volume-title":"J. Exp. Med.","year":"1997"},{"key":"2026012807134391700_R7","first-page":"3799","article-title":"Receptor activator of NF-\u03baB ligand and osteoprotegerin regulate proinflammatory cytokine production in mice","volume-title":"J. Immunol.","year":"2006"},{"key":"2026012807134391700_R8","first-page":"243","article-title":"Paracrine regulation of osteoclast formation and activity: milestones in discovery","volume-title":"J. Musculoskelet. Neuronal Interact.","year":"2004"},{"key":"2026012807134391700_R9","first-page":"144","article-title":"Activated T lymphocytes support osteoclast formation in vitro","volume-title":"Biochem. Biophys. Res. Commun.","year":"1999"},{"key":"2026012807134391700_R10","first-page":"188","article-title":"Osteoprotegerin ligand: a common link between osteoclastogenesis, lymph node formation and lymphocyte development","volume-title":"Immunol. Cell Biol.","year":"1999"},{"key":"2026012807134391700_R11","first-page":"987","article-title":"B and T lymphocytes are the primary sources of RANKL in the bone resorptive lesion of periodontal disease","volume-title":"Am. J. Pathol.","year":"2006"},{"key":"2026012807134391700_R12","first-page":"2673","article-title":"Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction","volume-title":"J. Exp. Med.","year":"2006"},{"key":"2026012807134391700_R13","first-page":"1218","article-title":"The IL-23\/IL-17 axis in inflammation","volume-title":"J. Clin. Invest.","year":"2006"},{"key":"2026012807134391700_R14","first-page":"744","article-title":"Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain","volume-title":"Nature","year":"2003"},{"key":"2026012807134391700_R15","first-page":"984","article-title":"T-cells mediate an inhibitory effect of interleukin-4 on osteoclastogenesis","volume-title":"J. Bone Miner. Res.","year":"2003"},{"key":"2026012807134391700_R16","first-page":"595","article-title":"Interleukin 18 inhibits osteoclast formation via T cell production of granulocyte macrophage colony-stimulating factor","volume-title":"J. Clin. Invest.","year":"1998"},{"key":"2026012807134391700_R17","first-page":"4915","article-title":"IL-12 alone and in synergy with IL-18 inhibits osteoclast formation in vitro","volume-title":"J. Immunol.","year":"2001"},{"key":"2026012807134391700_R18","first-page":"317","article-title":"Immunosuppressant drugs and bone disease: a clinician\u2019s perspective","volume-title":"J. Clin. Densitom.","year":"1998"},{"key":"2026012807134391700_R19","first-page":"361","article-title":"The biology of IL-12: coordinating innate and adaptive immune responses","volume-title":"Cytokine Growth Factor Rev.","year":"2003"},{"key":"2026012807134391700_R20","first-page":"1113","article-title":"The costimulatory effect of IL-18 on the induction of antigen-specific IFN-\u03b3 production by resting T cells is IL-12 dependent and is mediated by up-regulation of the IL-12 receptor \u03b22 subunit","volume-title":"Eur. J. Immunol.","year":"2000"},{"key":"2026012807134391700_R21","first-page":"5699","article-title":"A receptor for the heterodimeric cytokine IL-23 is composed of IL-12R\u03b21 and a novel cytokine receptor subunit, IL-23R","volume-title":"J. Immunol.","year":"2002"},{"key":"2026012807134391700_R22","first-page":"4662","article-title":"IL-17 production is dominated by \u03b3\u03b4 T cells rather than CD4 T cells during Mycobacterium tuberculosis infection","volume-title":"J. Immunol.","year":"2006"},{"key":"2026012807134391700_R23","first-page":"2827","article-title":"Compromised humoral and delayed-type hypersensitivity responses in IL-23-deficient mice","volume-title":"J. Immunol.","year":"2004"},{"key":"2026012807134391700_R24","first-page":"761","article-title":"Divergent roles of IL-23 and IL-12 in host defense against Klebsiella pneumoniae","volume-title":"J. Exp. Med.","year":"2005"},{"key":"2026012807134391700_R25","first-page":"1910","article-title":"Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17","volume-title":"J. Biol. Chem.","year":"2003"},{"key":"2026012807134391700_R26","first-page":"164","article-title":"The generation of highly enriched osteoclast-lineage cell populations","volume-title":"Bone","year":"2002"},{"key":"2026012807134391700_R27","first-page":"158","article-title":"Differentiation potential of a mouse bone marrow stromal cell line","volume-title":"J. Cell. Biochem.","year":"2003"},{"key":"2026012807134391700_R28","first-page":"9420","article-title":"Rapidly forming apatitic mineral in an osteoblastic cell line (UMR 106-01 BSP)","volume-title":"J. Biol. Chem.","year":"1995"},{"key":"2026012807134391700_R29","first-page":"1873","article-title":"Secreted frizzled-related protein-1 inhibits RANKL-dependent osteoclast formation","volume-title":"J. Bone Miner. Res.","year":"2004"},{"key":"2026012807134391700_R30","first-page":"1","article-title":"A PCR primer bank for quantitative gene expression analysis","volume-title":"Nucleic Acids Res.","year":"2003"},{"key":"2026012807134391700_R31","first-page":"E456","article-title":"Perinatal testosterone surge is required for normal adult bone size but not for normal bone remodeling","volume-title":"Am. J. Physiol.","year":"2006"},{"key":"2026012807134391700_R32","first-page":"1095","article-title":"Bone homeostasis in growth hormone receptor-null mice is restored by IGF-I but independent of Stat5","volume-title":"J. Clin. Invest.","year":"2000"},{"key":"2026012807134391700_R33","first-page":"1093","article-title":"Interleukin-11 receptor signaling is required for normal bone remodeling","volume-title":"J. Bone Miner Res.","year":"2005"},{"key":"2026012807134391700_R34","first-page":"977","article-title":"Replication of an association between IL23R gene polymorphism with inflammatory bowel disease","volume-title":"Clin. Gastroenterol. Hepatol.","year":"2007"},{"key":"2026012807134391700_R35","first-page":"99","article-title":"Association analysis of IL-12B and IL-23R polymorphisms in myocardial infarction","volume-title":"J. Mol. Med.","year":"2007"},{"key":"2026012807134391700_R36","first-page":"273","article-title":"A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes","volume-title":"Am. J. Hum. Genet.","year":"2007"},{"key":"2026012807134391700_R37","first-page":"132","article-title":"Breakthroughs in genetic studies of ankylosing spondylitis","volume-title":"Rheumatology","year":"2008"},{"key":"2026012807134391700_R38","first-page":"610","article-title":"Severe osteoporosis in mice lacking osteoclastogenesis inhibitory factor\/osteoprotegerin","volume-title":"Biochem. Biophys. Res. Commun.","year":"1998"},{"key":"2026012807134391700_R39","first-page":"6852","article-title":"CD8+ IL-17-producing T cells are important in effector functions for the elicitation of contact hypersensitivity responses","volume-title":"J. Immunol.","year":"2006"},{"key":"2026012807134391700_R40","first-page":"5245","article-title":"Granulocyte-macrophage colony-stimulating factor (CSF) and macrophage CSF-dependent macrophage phenotypes display differences in cytokine profiles and transcription factor activities: implications for CSF blockade in inflammation","volume-title":"J. Immunol.","year":"2007"},{"key":"2026012807134391700_R41","first-page":"977","article-title":"Role of colony-stimulating factors in osteoclast development","volume-title":"J. Bone Miner. Res.","year":"1991"},{"key":"2026012807134391700_R42","first-page":"190","article-title":"Osteoclastic potential of human CFU-GM: biphasic effect of GM-CSF","volume-title":"J. Bone Miner. Res.","year":"2004"},{"key":"2026012807134391700_R43","first-page":"1345","article-title":"IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis","volume-title":"J. Clin. Invest.","year":"1999"},{"key":"2026012807134391700_R44","first-page":"285","article-title":"Phagocytosis of apoptotic neutrophils regulates granulopoiesis via IL-23 and IL-17","volume-title":"Immunity","year":"2005"},{"key":"2026012807134391700_R45","first-page":"675","article-title":"Transgenic mice expressing a hemopoietic growth factor gene (GM-CSF) develop accumulations of macrophages, blindness, and a fatal syndrome of tissue damage","volume-title":"Cell","year":"1987"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/181\/8\/5720\/62581284\/7932.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/181\/8\/5720\/62581284\/7932.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T12:16:35Z","timestamp":1769602595000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/181\/8\/5720\/8009206"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,10]]},"references-count":45,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2008,10,15]]},"published-print":{"date-parts":[[2008,10,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.181.8.5720","relation":{},"ISSN":["1550-6606","0022-1767"],"issn-type":[{"value":"1550-6606","type":"electronic"},{"value":"0022-1767","type":"print"}],"subject":[],"published-other":{"date-parts":[[2008,10]]},"published":{"date-parts":[[2008,10]]}}}