{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:00:33Z","timestamp":1772118033746,"version":"3.50.1"},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,3,28]],"date-time":"2013-03-28T00:00:00Z","timestamp":1364428800000},"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":[[2013,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To analyze whether the expression and modulation of T cell receptor (TCR) signaling is dependent on Casitas B lineage lymphoma b (Cbl\u2010b) in T cells from patients with systemic lupus erythematosus (SLE) upon stimulation with a tolerogenic substance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Peripheral blood mononuclear cells were obtained from 20 patients with SLE (active disease or in remission) and 20 healthy controls. Levels of Cbl\u2010b expression were measured using reverse transcription\u2013polymerase chain reaction and Western blotting in peripheral CD4+ T cells from SLE patients and healthy controls upon anergy induction. Cell proliferation was measured using the carboxyfluorescein diacetate succinimidyl ester dilution method. Cytokine production was analyzed by luminometry, and surface expression of activation markers was assessed by flow cytometry. Transfection assays were performed to induce overexpression of Cbl\u2010b, and phosphorylation of TCR\u2010associated kinases was evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CD4+ T cells from SLE patients displayed resistance to anergy (as evidenced by increased cell proliferation, interleukin\u20102 production, and expression of activation and costimulatory markers), and this was associated with altered Cbl\u2010b expression. Upon ionomycin treatment, primary T cells showed enhanced MAPK activity and decreased Akt phosphorylation, which was representative of the anergic state. In T cells from lupus patients, Cbl\u2010b overexpression led to increased expression of phosphorylated MAPK, thus indicating the reversibility of anergy resistance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings suggest that abnormal peripheral tolerance in SLE is caused by a deficiency in Cbl\u2010b, and that this ubiquitin ligase plays a key role in regulating TCR signaling during the induction of peripheral tolerance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.37833","type":"journal-article","created":{"date-parts":[[2012,12,22]],"date-time":"2012-12-22T01:15:32Z","timestamp":1356138932000},"page":"1032-1042","source":"Crossref","is-referenced-by-count":15,"title":["Casitas B Lineage Lymphoma b Is a Key Regulator of Peripheral Tolerance in Systemic Lupus Erythematosus"],"prefix":"10.1002","volume":"65","author":[{"given":"Diana","family":"G\u00f3mez\u2010Mart\u00edn","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"Ibarra\u2010S\u00e1nchez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge","family":"Romo\u2010Tena","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9","family":"Cruz\u2010Ru\u00edz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9","family":"Esparza\u2010L\u00f3pez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel","family":"Galindo\u2010Campos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariana","family":"D\u00edaz\u2010Zamudio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge","family":"Alcocer\u2010Varela","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,3,28]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1731"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M604192200"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1047"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00767-5"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.22.012703.104813"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2004.07.013"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/35003235"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni0901-870"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/35003228"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.193.3.329"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2007.12.003"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.21.120601.141110"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.6.4216"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.2.741"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.11.6627"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780251101"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780350606"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/0471142735.im0409s84"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1177\/0961203307088307"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202499"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI110579"},{"key":"e_1_2_7_24_2","doi-asserted-by":"crossref","first-page":"2651","DOI":"10.4049\/jimmunol.130.6.2651","article-title":"Defective 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