{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T15:47:59Z","timestamp":1790610479072,"version":"4.1.0"},"reference-count":83,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunological Reviews"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Citrullination and deamidation are post\u2010translational modifications (PTMs) increasingly recognized as important contributors to neoepitope formation in type 1 diabetes (T1D). Under inflammatory and endoplasmic reticulum stress conditions, beta cells activate calcium\u2010dependent peptidylarginine deiminase and transglutaminase enzymes, leading to self\u2010protein modification, altered peptide charge and HLA\u2010binding properties, thereby generating neoepitopes that can be recognized by autoreactive CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Accumulating evidence from both murine and human studies demonstrates that immune responses against citrullinated and deamidated beta cell proteins are present and increase with disease progression, supporting a role in epitope spreading rather than disease initiation. Although both PTMs are biochemically analogous, their kinetics and regulation are distinct: citrullination appears as an earlier and partly intrinsic response of stressed beta cells, whereas deamidation is more closely associated with sustained inflammation and later disease stages. In parallel, reduced PTM\u2010generating enzyme expression in the thymus may limit central tolerance to modified epitopes, facilitating escape of autoreactive T cells. In this review, we summarize current insights into the biochemical and immunological roles of citrullination and deamidation in T1D, with emphasis on their temporal regulation, contribution to neoepitope formation, and potential as therapeutic targets, highlighting key findings from our own work in the field.\n                  <\/jats:p>","DOI":"10.1111\/imr.70158","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T05:10:13Z","timestamp":1785993013000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Citrullination and Deamidation in Type 1 Diabetes: Linking Beta Cell Stress to Neoantigen\u2010Driven Autoimmunity"],"prefix":"10.1111","volume":"341","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6246-0088","authenticated-orcid":false,"given":"A\u00efsha","family":"Callebaut","sequence":"first","affiliation":[{"name":"Center for Translational Immunology Benaroya Research 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Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7126-356X","authenticated-orcid":false,"given":"Lut","family":"Overbergh","sequence":"additional","affiliation":[{"name":"Laboratory for Clinical and Experimental Endocrinology KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2009.21"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399\u20100039.2003.00152.x"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/347151a0"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115573"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.2337\/diab.45.10.1344"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2009\u20101257"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2015.00067"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M700085\u2010MCP200"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2016.04.009"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010012\u20102762\u20103"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2017.05.013"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2016.30"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20051251"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.2337\/db13\u20101952"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.2337\/db14\u20100621"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.2337\/db12\u20100112"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4203"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.2337\/db12\u20101214"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad2791"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2016.10.007"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2007\u20100015"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2011.08.006"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.2337\/db11\u20101675"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11892\u2010015\u20100657\u20107"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2013.10.003"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2024.101355"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000452"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389450116666150202160954"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2012.09.029"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagrm.2013.07.003"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.124729"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2003.012211"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.10357"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2007.01.054"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/cb500933j"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11274\u2010019\u20102791\u2010x"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20021234"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281\u2010012\u20100305\u20100"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1014"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.20.11991"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.119.2.463"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.1.148\u2010155.2001"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M009862200"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21030791"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0050327"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)75724-X"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.624590"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.2337\/db11\u20101293"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010016\u20104191\u20101"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc15\u20102849"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.07.007"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2023.101809"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.2337\/db20\u20100421"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.2337\/db18\u20100295"},{"key":"e_1_2_11_56_1","doi-asserted-by"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