{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T08:13:58Z","timestamp":1777623238103,"version":"3.51.4"},"reference-count":24,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2012,11,28]],"date-time":"2012-11-28T00:00:00Z","timestamp":1354060800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To elucidate the role of tumor necrosis factor \u03b1\u2013induced adipose\u2010related protein (TIARP; or tumor necrosis factor \u03b1\u2013induced protein 9 [TNFAIP\u20109]) in the development and pathogenesis of arthritis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We generated TIARP\u2010deficient (TIARP<jats:sup>\u2212\/\u2212<\/jats:sup>) mice and investigated several organs in aged mice. Peritoneal macrophages were collected and cultured with lipopolysaccharide (LPS) and TNF\u03b1, and then the production of cytokines and subsequent NF\u2010\u03baB signal transduction were analyzed. We also examined the susceptibility of young TIARP<jats:sup>\u2212\/\u2212<\/jats:sup> mice to collagen\u2010induced arthritis (CIA). Draining lymph nodes and splenocytes were isolated and cultured, and serum levels of anti\u2013type II collagen (anti\u2010CII) antibodies, interleukin\u20106 (IL\u20106), and TNF\u03b1 on day 60 were measured. We further investigated the effects of anti\u2013IL\u20106 receptor monoclonal antibody (mAb) on the development of arthritis in TIARP<jats:sup>\u2212\/\u2212<\/jats:sup> mice. IL\u20106\/STAT\u20103 signaling was also analyzed using TIARP<jats:sup>\u2212\/\u2212<\/jats:sup> macrophages.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>TIARP<jats:sup>\u2212\/\u2212<\/jats:sup> mice developed spontaneous enthesitis and synovitis, had high serum levels of IL\u20106, had increased CD11b+ cell counts in the spleen, and showed enhanced LPS\u2010 and TNF\u03b1\u2010induced IL\u20106 expression in macrophages. Sustained degradation of I\u03baB\u03b1 with dysregulated apoptosis was also noted in TIARP<jats:sup>\u2212\/\u2212<\/jats:sup> macrophages. CIA was clearly exacerbated in TIARP<jats:sup>\u2212\/\u2212<\/jats:sup> mice, accompanied by marked neutrophil and macrophage infiltration in joints. The levels of anti\u2010CII antibodies in serum were unchanged, whereas autoreactive Th1 cell and Th17 cell responses were higher in TIARP<jats:sup>\u2212\/\u2212<\/jats:sup> mice. Treatment with anti\u2013IL\u20106 receptor mAb prevented the development of CIA in TIARP<jats:sup>\u2212\/\u2212<\/jats:sup> mice, and TIARP<jats:sup>\u2212\/\u2212<\/jats:sup> macrophages showed increased IL\u20106\u2013induced STAT\u20103 phosphorylation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings suggest that TIARP acts as a negative regulator of arthritis by suppressing IL\u20106 production, its signaling and TNF\u03b1\u2010induced NF\u2010\u03baB signaling, resulting in enhanced apoptosis in macrophages.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.34666","type":"journal-article","created":{"date-parts":[[2012,8,8]],"date-time":"2012-08-08T17:05:18Z","timestamp":1344445518000},"page":"3877-3885","source":"Crossref","is-referenced-by-count":17,"title":["Murine tumor necrosis factor \u03b1\u2013induced adipose\u2010related protein (tumor necrosis factor \u03b1\u2013induced protein 9) deficiency leads to arthritis via interleukin\u20106 overproduction with enhanced NF\u2010\u03baB, STAT\u20103 signaling, and dysregulated apoptosis of macrophages"],"prefix":"10.1002","volume":"64","author":[{"given":"Asuka","family":"Inoue","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isao","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoko","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoto","family":"Umeda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiko","family":"Mihara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoru","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takayuki","family":"Sumida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,11,28]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2009.181"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0b013e3283295fec"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5445.1732"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.7.4503"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar2437"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.23222"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar2779"},{"key":"e_1_2_7_9_2","first-page":"99","article-title":"Six\u2010transmembrane epithelial antigen of prostate 4 (STEAP4) is expressed on monocytes\/neutrophils, and is regulated by TNF antagonist in patients with rheumatoid arthritis","volume":"30","author":"Tanaka Y","year":"2012","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.02.049"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199812)41:12<2117::AID-ART6>3.0.CO;2-P"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M105726200"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(04)00096-1"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-02-003681"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-11-226"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.066936"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.2010.02288.x"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.04.022"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2007.27"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2007.32"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.874"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21394"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020619"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20100900"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.3109\/s10165-011-0475-y"}],"container-title":["Arthritis &amp; 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