{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T19:23:19Z","timestamp":1780082599594,"version":"3.54.0"},"reference-count":45,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2016,10,27]],"date-time":"2016-10-27T00:00:00Z","timestamp":1477526400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AR055646"],"award-info":[{"award-number":["AR055646"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000980","name":"Arthritis Foundation","doi-asserted-by":"publisher","award":["CRTA #5926"],"award-info":[{"award-number":["CRTA #5926"]}],"id":[{"id":"10.13039\/100000980","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>In lupus nephritis, tubulointerstitial inflammation (TII) is associated with in situ adaptive immune cell networks that amplify local tissue damage. Since conventional therapy appears ineffective for severe TII, and these patients often progress to renal failure, understanding in situ mechanisms might reveal new therapeutic targets. This study was undertaken to assess whether dysregulated apoptotic regulators maintain local adaptive immunity and drive inflammation in TII.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study utilized novel computational approaches that, when applied to multicolor confocal images, quantified apoptotic regulator protein expression in selected lymphocyte subsets. This approach was validated using laser\u2010capture microdissection (LCM) coupled to quantitative polymerase chain reaction (qPCR). Furthermore, the consequences of dysregulated apoptotic mediator expression were explored in a murine model of lupus nephritis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Analyses of renal biopsy tissue from patients with lupus nephritis and those with mixed cellular renal allograft rejection revealed that the B cell lymphoma 2 protein (Bcl\u20102) was frequently expressed in infiltrating lymphocytes, whereas expression of myeloid cell leukemia 1 was low. In contrast, the reciprocal pattern of expression was observed in tonsil germinal centers. These results were consistent with RNA expression data obtained using LCM and qPCR. Bcl\u20102 was also highly expressed in tubulointerstitial infiltrates in (NZB \u00d7 NZW)F1 (NZB\/NZW) mice. Furthermore, treatment of NZB\/NZW mice with ABT\u2010199, a selective oral inhibitor of Bcl\u20102, prolonged survival and prevented proteinuria and development of TII in a lupus prevention model. Interestingly, glomerular immune complexes were partially ameliorated by ABT\u2010199 treatment, and serum anti\u2013double\u2010stranded DNA antibody titers were unaffected.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These data demonstrate that Bcl\u20102 is an attractive therapeutic target in patients with lupus nephritis who manifest TII.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.39744","type":"journal-article","created":{"date-parts":[[2016,5,9]],"date-time":"2016-05-09T15:54:48Z","timestamp":1462809288000},"page":"2740-2751","source":"Crossref","is-referenced-by-count":26,"title":["Bcl\u20102 as a Therapeutic Target in Human Tubulointerstitial Inflammation"],"prefix":"10.1002","volume":"68","author":[{"given":"Kichul","family":"Ko","sequence":"first","affiliation":[{"name":"University of Chicago Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianing","family":"Wang","sequence":"additional","affiliation":[{"name":"University of Chicago Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart","family":"Perper","sequence":"additional","affiliation":[{"name":"Stuart Perper, BS, Susan Westmoreland, VMD, Lisa Olson, PhD, Li Chun Wang, PhD: AbbVie AbbVie Bioresearch Center Worcester Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulei","family":"Jiang","sequence":"additional","affiliation":[{"name":"University of Chicago Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denisse","family":"Yanez","sequence":"additional","affiliation":[{"name":"University of Chicago Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalya","family":"Kaverina","sequence":"additional","affiliation":[{"name":"University of Chicago Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junting","family":"Ai","sequence":"additional","affiliation":[{"name":"University of Chicago Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir M.","family":"Liarski","sequence":"additional","affiliation":[{"name":"University of Chicago Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6877-5510","authenticated-orcid":false,"given":"Anthony","family":"Chang","sequence":"additional","affiliation":[{"name":"University of Chicago Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2520-1170","authenticated-orcid":false,"given":"Yahui","family":"Peng","sequence":"additional","affiliation":[{"name":"University of Chicago Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Lan","sequence":"additional","affiliation":[{"name":"University of Chicago Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Westmoreland","sequence":"additional","affiliation":[{"name":"Stuart Perper, BS, Susan Westmoreland, VMD, Lisa Olson, PhD, Li Chun Wang, PhD: AbbVie AbbVie Bioresearch Center Worcester Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Olson","sequence":"additional","affiliation":[{"name":"Stuart Perper, BS, Susan Westmoreland, VMD, Lisa Olson, PhD, Li Chun Wang, PhD: AbbVie AbbVie Bioresearch Center Worcester Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryellen L.","family":"Giger","sequence":"additional","affiliation":[{"name":"University of Chicago Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Chun Wang","sequence":"additional","affiliation":[{"name":"Stuart Perper, BS, Susan Westmoreland, VMD, Lisa Olson, PhD, Li Chun Wang, PhD: AbbVie AbbVie Bioresearch Center Worcester Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus R.","family":"Clark","sequence":"additional","affiliation":[{"name":"University of Chicago Chicago Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,10,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20042251"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2308"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1568"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.19.8661"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1006\/jaut.1994.1046"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780371004"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/17402520600877786"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.10.026"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.12.012"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.md.0000091181.93122.55"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21955"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.20441"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001983"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1995.487"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1797.2005.00397.x"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2006.03219.x"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.3.971"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-005-4084-4"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3008146"},{"key":"e_1_2_7_21_1","first-page":"1","article-title":"Computerized image analysis of cell\u2010cell interactions in human renal tissue by using multi\u2010channel immunoflourescent confocal microscopy","volume":"8315","author":"Peng Y","year":"2012","journal-title":"Proc SPIE"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfg034"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3249"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0802813"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-2478(02)00003-2"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V83.7.1856.1856"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V91.1.244"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1191793"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-05-091306"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/271694"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1191\/0961203302lu158oa"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60954-X"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-203455"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2527"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4402182"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0902927"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI108626"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1995.341"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4400724"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.9.2778"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199812)28:12<4418::AID-IMMU4418>3.0.CO;2-7"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02067"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.01.037"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38966"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3919"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2006090992"}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.39744","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.39744","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.39744","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T18:32:38Z","timestamp":1759948358000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.39744"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,10,27]]},"references-count":45,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2016,11]]}},"alternative-id":["10.1002\/art.39744"],"URL":"https:\/\/doi.org\/10.1002\/art.39744","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,10,27]]}}}