{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T16:49:42Z","timestamp":1793724582069,"version":"4.6.1"},"reference-count":32,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2012,6,26]],"date-time":"2012-06-26T00:00:00Z","timestamp":1340668800000},"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":[[2012,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To define the role of indoleamine 2,3\u2010dioxygenase (IDO) in driving pathogenic B cell responses that lead to arthritis and to determine if inhibitors of the IDO pathway can be used in conjunction with therapeutic B cell depletion to prevent the reemergence of autoantibodies and arthritis following reconstitution of the B cell repertoire.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Immunoglobulin\u2010transgenic mice were treated with the IDO inhibitor 1\u2010methyltryptophan (1\u2010MT) and monitored for the extent of autoreactive B cell activation. Arthritic K\/BxN mice were treated with B cell depletion alone or in combination with 1\u2010MT. Mice were monitored for the presence of autoantibody\u2010secreting cells, inflammatory cytokines, and joint inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Treatment with 1\u2010MT did not affect the initial activation or survival of autoreactive B cells, but it did inhibit their ability to differentiate into autoantibody\u2010secreting cells. Treatment with anti\u2010CD20 depleted the B cell repertoire and attenuated arthritis symptoms; however, the arthritis symptoms rapidly returned as B cells repopulated the repertoire. Administration of 1\u2010MT prior to B cell repopulation prevented the production of autoantibodies and inflammatory cytokines and flare of arthritis symptoms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>IDO activity is essential for the differentiation of autoreactive B cells into antibody\u2010secreting cells, but it is not necessary for their initial stages of activation. Addition of 1\u2010MT to therapeutic B cell depletion prevents the differentiation of autoantibody\u2010secreting cells and the recurrence of autoimmune arthritis following reconstitution of the B cell repertoire. These data suggest that IDO inhibitors could be used in conjunction with B cell depletion as an effective cotherapeutic strategy in the treatment of rheumatoid arthritis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.34406","type":"journal-article","created":{"date-parts":[[2012,1,31]],"date-time":"2012-01-31T15:40:28Z","timestamp":1328024428000},"page":"2169-2178","source":"Crossref","is-referenced-by-count":26,"title":["Addition of an indoleamine 2,3,\u2010dioxygenase inhibitor to B cell\u2013depletion therapy blocks autoreactive B cell activation and recurrence of arthritis in K\/BxN mice"],"prefix":"10.1002","volume":"64","author":[{"given":"Elizabeth","family":"Pigott","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Mandik\u2010Nayak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,6,26]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197509112931101"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/anr.1780320104"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0b013e3283369cb8"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.berh.2006.05.010"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21650"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0709205105"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.7.4994"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21617"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.23473"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0804328"},{"key":"e_1_2_7_12_2","doi-asserted-by":"crossref","first-page":"4700","DOI":"10.1016\/S0021-9258(17)30447-7","article-title":"Indoleamine 2,3\u2010dioxygenase: purification and some properties","volume":"253","author":"Shimizu T","year":"1978","journal-title":"J Biol Chem"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-005-0056-6"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81989-3"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20060701"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5445.1732"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.182549099"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.5.3351"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1001074107"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.2.1369"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81109-5"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-0135-0_3"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1457"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1711.2003.t01-1-01177.x"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2163"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1097\/PPO.0b013e3181eb3343"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(02)00176-5"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2003.08.031"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar2205"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.2174\/092986711795656072"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.11181"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.144998"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2010.08076.x"}],"container-title":["Arthritis &amp; 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