{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T15:48:02Z","timestamp":1790610482247,"version":"4.1.0"},"reference-count":40,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,6]],"date-time":"2021-02-06T00:00:00Z","timestamp":1612569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100003185","name":"National Psoriasis Foundation","doi-asserted-by":"publisher","award":["Translational Grant 2019-2021"],"award-info":[{"award-number":["Translational Grant 2019-2021"]}],"id":[{"id":"10.13039\/100003185","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ricerca Finalizzata","award":["CO-2018"],"award-info":[{"award-number":["CO-2018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>LL37 acts as T-cell\/B-cell autoantigen in Systemic lupus erythematosus (SLE) and psoriatic disease. Moreover, when bound to \u201cself\u201d nucleic acids, LL37 acts as \u201cdanger signal,\u201d leading to type I interferon (IFN-I)\/pro-inflammatory factors production. T-cell epitopes derived from citrullinated-LL37 act as better antigens than unmodified LL37 epitopes in SLE, at least in selected HLA-backgrounds, included the SLE-associated HLA-DRB1*1501\/HLA-DRB5*0101 backgrounds. Remarkably, while \u201cfully-citrullinated\u201d LL37 acts as better T-cell-stimulator, it loses DNA-binding ability and the associated \u201cadjuvant-like\u201d properties. Since LL37 undergoes a further irreversible post-translational modification, carbamylation and antibodies to carbamylated self-proteins other than LL37 are present in SLE, here we addressed the involvement of carbamylated-LL37 in autoimmunity and inflammation in SLE. We detected carbamylated-LL37 in SLE-affected tissues. Most importantly, carbamylated-LL37-specific antibodies and CD4 T-cells circulate in SLE and both correlate with disease activity. In contrast to \u201cfully citrullinated-LL37,\u201d \u201cfully carbamylated-LL37\u201d maintains both innate and adaptive immune-cells\u2019 stimulatory abilities: in complex with DNA, carbamylated-LL37 stimulates plasmacytoid dendritic cell IFN-\u03b1 production and B-cell maturation into plasma cells. Thus, we report a further example of how different post-translational modifications of a self-antigen exert complementary effects that sustain autoimmunity and inflammation, respectively. These data also show that T\/B-cell responses to carbamylated-LL37 represent novel SLE disease biomarkers.<\/jats:p>","DOI":"10.3390\/ijms22041650","type":"journal-article","created":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T20:51:51Z","timestamp":1612817511000},"page":"1650","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Complementary Effects of Carbamylated and Citrullinated LL37 in Autoimmunity and Inflammation in Systemic Lupus Erythematosus"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8398-4567","authenticated-orcid":false,"given":"Roberto","family":"Lande","sequence":"first","affiliation":[{"name":"Pharmacological Research and Experimental Therapy Unit, National Centre for Pre-Clinical and Clinical Drug Research and Evaluation, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Immacolata","family":"Pietraforte","sequence":"additional","affiliation":[{"name":"Department of Oncology and Molecular Medicine, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3870-5332","authenticated-orcid":false,"given":"Anna","family":"Mennella","sequence":"additional","affiliation":[{"name":"Pharmacological Research and Experimental Therapy Unit, National Centre for Pre-Clinical and Clinical Drug Research and Evaluation, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"},{"name":"Department of Dermatology, University Hospital CHUV, 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Palazzo","sequence":"additional","affiliation":[{"name":"Pharmacological Research and Experimental Therapy Unit, National Centre for Pre-Clinical and Clinical Drug Research and Evaluation, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1969-2097","authenticated-orcid":false,"given":"Francesca Romana","family":"Spinelli","sequence":"additional","affiliation":[{"name":"Department of Clinical and Internistic Sciences, Anesthesiology and Cardiovascular Sciences, University Sapienza, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Giannakakis","sequence":"additional","affiliation":[{"name":"Department of Pathology, University Sapienza, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6610-350X","authenticated-orcid":false,"given":"Francesca","family":"Spadaro","sequence":"additional","affiliation":[{"name":"Confocal Microscopy UNIT, Core Facilities, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Falchi","sequence":"additional","affiliation":[{"name":"National AIDS Center, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Riccieri","sequence":"additional","affiliation":[{"name":"Department of Clinical and Internistic Sciences, Anesthesiology and Cardiovascular Sciences, University Sapienza, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Stefanantoni","sequence":"additional","affiliation":[{"name":"Department of Clinical and Internistic Sciences, Anesthesiology and Cardiovascular Sciences, University Sapienza, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2547-3440","authenticated-orcid":false,"given":"Curdin","family":"Conrad","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital CHUV, 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiano","family":"Alessandri","sequence":"additional","affiliation":[{"name":"Department of Clinical and Internistic Sciences, Anesthesiology and Cardiovascular Sciences, University Sapienza, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Conti","sequence":"additional","affiliation":[{"name":"Department of Clinical and Internistic Sciences, Anesthesiology and Cardiovascular Sciences, University Sapienza, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6924-3826","authenticated-orcid":false,"given":"Loredana","family":"Frasca","sequence":"additional","affiliation":[{"name":"Pharmacological Research and Experimental Therapy Unit, National Centre for Pre-Clinical and Clinical Drug Research and Evaluation, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1056\/NEJMra1100359","article-title":"Systemic lupus erythematosus","volume":"365","author":"Tsokos","year":"2011","journal-title":"N. 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