{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T10:50:34Z","timestamp":1779187834881,"version":"3.51.4"},"reference-count":45,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,4,26]],"date-time":"2020-04-26T00:00:00Z","timestamp":1587859200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Fc\u03b3 receptors (Fc\u03b3R) play important roles in both protective and pathogenic immune responses. The assembly of the CBM signalosome encompassing caspase recruitment domain\u2013containing protein 9, B cell CLL\/lymphoma 10, and mucosa\u2010associated lymphoid tissue lymphoma translocation protein 1 (MALT\u20101) is required for optimal Fc\u03b3R\u2010induced canonical NF\u2010\u03baB activation and proinflammatory cytokine release. This study was undertaken to clarify the relevance of <jats:styled-content style=\"fixed-case\">MALT<\/jats:styled-content>\u20101 protease activity in Fc\u03b3R\u2010driven events and evaluate the therapeutic potential of selective <jats:styled-content style=\"fixed-case\">MALT<\/jats:styled-content>\u20101 protease inhibitors in Fc\u03b3R\u2010mediated diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using genetic and pharmacologic disruption of <jats:styled-content style=\"fixed-case\">MALT<\/jats:styled-content>\u20101 scaffolding and enzymatic activity, we assessed the relevance of <jats:styled-content style=\"fixed-case\">MALT<\/jats:styled-content>\u20101 function in murine and human primary myeloid cells upon stimulation with immune complexes (<jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content>s) and in murine models of autoantibody\u2010driven arthritis and immune thrombocytopenic purpura (<jats:styled-content style=\"fixed-case\">ITP<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">MALT<\/jats:styled-content>\u20101 protease function is essential for optimal Fc\u03b3R\u2010induced production of proinflammatory cytokines by various murine and human myeloid cells stimulated with <jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content>s. In contrast, <jats:styled-content style=\"fixed-case\">MALT<\/jats:styled-content>\u20101 protease inhibition did not affect the Syk\u2010dependent, Fc\u03b3R\u2010mediated production of reactive oxygen species or leukotriene B<jats:sub>4<\/jats:sub>. Notably, pharmacologic <jats:styled-content style=\"fixed-case\">MALT<\/jats:styled-content>\u20101 protease inhibition in vivo reduced joint inflammation in the murine K\/BxN serum\u2013induced arthritis model (mean area under the curve for paw swelling of 45.42% versus 100% in control mice; <jats:italic>P<\/jats:italic> = 0.0007) but did not affect platelet depletion in a passive model of <jats:styled-content style=\"fixed-case\">ITP<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings indicate a specific contribution of <jats:styled-content style=\"fixed-case\">MALT<\/jats:styled-content>\u20101 protease activity to Fc\u03b3R\u2010mediated events and suggest that <jats:styled-content style=\"fixed-case\">MALT<\/jats:styled-content>\u20101 protease inhibitors have therapeutic potential in a subset of Fc\u03b3R\u2010driven inflammatory disorders.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41204","type":"journal-article","created":{"date-parts":[[2020,1,13]],"date-time":"2020-01-13T08:05:35Z","timestamp":1578902735000},"page":"919-930","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Requirement of Mucosa\u2010Associated Lymphoid Tissue Lymphoma Translocation Protein 1 Protease Activity for Fc\u03b3 Receptor\u2013Induced Arthritis, but Not Fc\u03b3 Receptor\u2013Mediated Platelet Elimination, in Mice"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5344-0964","authenticated-orcid":false,"given":"Kea","family":"Martin","sequence":"first","affiliation":[{"name":"Novartis Institutes for BioMedical Research  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ratiba","family":"Touil","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grozdan","family":"Cvijetic","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Israel","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yeter","family":"Kolb","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie","family":"Sarret","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"St\u00e9phanie","family":"Valeaux","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Degl'Innocenti","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Le Meur","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadja","family":"Caesar","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maureen","family":"Bardet","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Beerli","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans\u2010Guenter","family":"Zerwes","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiri","family":"Kovarik","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Beltz","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Achim","family":"Schlapbach","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean","family":"Quancard","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine H.","family":"R\u00e9gnier","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Bigaud","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias","family":"Junt","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grazyna","family":"Wieczorek","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"Isnardi","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda","family":"Littlewood\u2010Evans","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Bornancin","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Calzascia","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,4,26]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00811"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2909"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2206"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25125"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-015-2059-z"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.7.4373"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2016.01.003"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11004"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2018.01.028"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2015.12.004"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1402254"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.10.044"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201488987"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0127083"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-018-0222-1"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm5018863"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/1254792"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-014-1565-4"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24552"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20160061"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.20885"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/imcb.1018"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.3791\/58439"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04926"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1466"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.11.6604"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001259"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20051982"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27438"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-07-166439"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1801614"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01898"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1215-2"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10203-2"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar1446"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601563"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2015.05.008"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.41029"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2017.10.009"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.819"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23123144"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00880"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612821666150316123436"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.11.015"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.4A0915-405R"}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.41204","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.41204","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/art.41204","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.41204","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T16:40:54Z","timestamp":1759941654000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.41204"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,26]]},"references-count":45,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,6]]}},"alternative-id":["10.1002\/art.41204"],"URL":"https:\/\/doi.org\/10.1002\/art.41204","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,26]]},"assertion":[{"value":"2019-10-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}