{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T05:32:44Z","timestamp":1791955964526,"version":"4.3.4"},"reference-count":166,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2019,7,10]],"date-time":"2019-07-10T00:00:00Z","timestamp":1562716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Mucosal surfaces play a central role in the pathogenesis of rheumatoid arthritis (RA). Several risk factors, such as cigarette smoking, environmental pollution, and periodontitis interact with the host at the mucosal level, triggering immune system activation. Moreover, the alteration of microbiota homeostasis is gaining increased attention for its involvement in the disease pathogenesis, modulating the immune cell response at a local and subsequently at a systemic level. Currently, the onset of the clinical manifest arthritis is thought to be the last step of a series of pathogenic events lasting years. The positivity for anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF), in absence of symptoms, characterizes a preclinical phase of RA\u2014namely systemic autoimmune phase- which is at high risk for disease progression. Several immune abnormalities, such as local ACPA production, increased T cell polarization towards a pro-inflammatory phenotype, and innate immune cell activation can be documented in at-risk subjects. Many of these abnormalities are direct consequences of the interaction between the environment and the host, which takes place at the mucosal level. The purpose of this review is to describe the humoral and cellular immune abnormalities detected in subjects at risk of RA, highlighting their origin from the mucosa\u2013environment interaction.<\/jats:p>","DOI":"10.3390\/cells8070700","type":"journal-article","created":{"date-parts":[[2019,7,10]],"date-time":"2019-07-10T11:56:51Z","timestamp":1562759811000},"page":"700","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Mucosa\u2013Environment Interactions in the Pathogenesis of Rheumatoid Arthritis"],"prefix":"10.3390","volume":"8","author":[{"given":"Bruno","family":"Lucchino","sequence":"first","affiliation":[{"name":"Rheumatology Unit, Department of Internal Medicine and Medical Specialities, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca Romani","family":"Spinelli","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, Department of Internal Medicine and Medical Specialities, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Iannuccelli","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, Department of Internal Medicine and Medical Specialities, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Paola","family":"Guzzo","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, Department of Internal Medicine and Medical Specialities, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Conti","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, Department of Internal Medicine and Medical Specialities, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela Di","family":"Franco","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, Department of Internal Medicine and Medical Specialities, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1056\/NEJMra1004965","article-title":"The pathogenesis of rheumatoid arthritis","volume":"365","author":"McInnes","year":"2011","journal-title":"N. 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