{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T08:59:24Z","timestamp":1789981164570,"version":"4.0.1"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2015,7,1]],"date-time":"2015-07-01T00:00:00Z","timestamp":1435708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Systemic autoimmune diseases such as lupus affect multiple organs, usually in a diverse fashion where only certain organs are affected in individual patients. It is unclear whether the \u201clocal\u201d immune cells play a role in regulating tissue specificity in relation to disease heterogeneity in systemic autoimmune diseases. In this study, we used skin as a model to determine the role of tissue-resident dendritic cells (DCs) in local and systemic involvement within a systemic lupus disease model. Skin-resident DCs, namely, Langerhans cells (LCs), have been implicated in regulating tolerance or autoimmunity using elegant transgenic models, however, their role in local versus systemic immune regulation is unknown. We demonstrate that although lymphocytes from skin-draining lymph nodes of autoimmune-prone MRL\/MpJ-Faslpr\/lpr (MRL-lpr) mice react spontaneously to a physiological skin self-Ag desmoglein-3, epicutaneous applications of desmoglein-3 induced tolerance that is dependent on LCs. Inducible ablation of LCs in adult preclinical MRL-lpr and MRL\/MpJ-Fas+\/+ mice resulted in increased autoantibodies against skin Ags and markedly accelerated lupus dermatitis with increased local macrophage infiltration, but had no effect on systemic autoantibodies such as anti-dsDNA Abs or disease in other organs such as kidneys, lung, and liver. Furthermore, skin-draining lymph nodes of LC-ablated MRL-lpr mice had significantly fewer CD4+ T cells producing anti-inflammatory cytokine IL-10 than LC-intact controls. These results indicate that a skin-resident DC population regulates local tolerance in systemic lupus and emphasize the importance of the local immune milieu in preventing tissue-specific autoimmunity, yet have no effect on systemic autoimmunity.<\/jats:p>","DOI":"10.4049\/jimmunol.1402735","type":"journal-article","created":{"date-parts":[[2015,6,13]],"date-time":"2015-06-13T03:40:47Z","timestamp":1434166847000},"page":"464-476","source":"Crossref","is-referenced-by-count":35,"title":["Langerhans Cells Maintain Local Tissue Tolerance in a Model of Systemic Autoimmune Disease"],"prefix":"10.1093","volume":"195","author":[{"given":"Jennifer K","family":"King","sequence":"first","affiliation":[{"name":"Autoimmunity and Tolerance Laboratory, Division of Rheumatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles , Los Angeles, CA 90095"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael L","family":"Philips","sequence":"additional","affiliation":[{"name":"Autoimmunity and Tolerance Laboratory, Division of Rheumatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles , Los Angeles, CA 90095"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna U","family":"Eriksson","sequence":"additional","affiliation":[{"name":"Autoimmunity and Tolerance Laboratory, Division of Rheumatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles , Los Angeles, CA 90095"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J","family":"Kim","sequence":"additional","affiliation":[{"name":"Autoimmunity and Tolerance Laboratory, Division of Rheumatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles , Los Angeles, CA 90095"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramesh C","family":"Halder","sequence":"additional","affiliation":[{"name":"Autoimmunity and Tolerance Laboratory, Division of Rheumatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles , Los Angeles, CA 90095"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine J","family":"Lee","sequence":"additional","affiliation":[{"name":"Dirks\/Dougherty Laboratory for Cancer Research, Department of Translational Immunology, John Wayne Cancer Institute at Providence Saint John\u2019s Health Center , Santa Monica, CA 90404"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram Raj","family":"Singh","sequence":"additional","affiliation":[{"name":"Autoimmunity and Tolerance Laboratory, Division of Rheumatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles , Los Angeles, CA 90095"},{"name":"Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California , Los Angeles, Los Angeles, CA 90095"},{"name":"Molecular Toxicology Interdepartmental Program, David Geffen School of Medicine, University of California , Los Angeles, Los Angeles, CA 90095"},{"name":"Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California , Los Angeles, Los Angeles, CA 90095"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,7,15]]},"reference":[{"key":"2025030703425902000_r1","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/B978-1-4377-1893-5.00019-4","volume-title":"Dubois' Lupus Erythematosus and Related Syndromes","author":"Singh","year":"2013","edition":"8th Ed."},{"key":"2025030703425902000_r2","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1016\/j.immuni.2010.11.025","article-title":"Dendritic cells in lupus are not required for activation of T and B cells but promote their expansion, resulting in tissue damage","volume":"33","author":"Teichmann","year":"2010","journal-title":"Immunity"},{"key":"2025030703425902000_r3","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1038\/nri3477","article-title":"The role of dendritic cells in autoimmunity","volume":"13","author":"Ganguly","year":"2013","journal-title":"Nat. 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