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In this study, we report that NFAT1 regulates dendritic cell (DC) tolerance and suppresses systemic autoimmunity using the experimental autoimmune myasthenia gravis (EAMG) as a model. Myasthenia gravis and EAMG are T cell\u2013dependent, Ab-mediated autoimmune disorders in which the acetylcholine receptor is the major autoantigen. NFAT1-knockout mice showed higher susceptibility to EAMG development with enhanced Th1\/Th17 cell responses. NFAT1 deficiency led to a phenotypic alteration of DCs that show hyperactivation of NF-\u03baB\u2013mediated signaling pathways and enhanced binding of NF-\u03baB (p50) to the promoters of IL-6 and IL-12. As a result, NFAT1-knockout DCs produced much higher levels of proinflammatory cytokines such as IL-1\u03b2, IL-6, IL-12, and TNF-\u03b1, which preferentially induce Th1\/Th17 cell differentiation. Our data suggest that NFAT1 may limit the hyperactivation of the NF-\u03baB\u2013mediated proinflammatory response in DCs and suppress autoimmunity by serving as a key regulator of DC tolerance.<\/jats:p>","DOI":"10.4049\/jimmunol.1700882","type":"journal-article","created":{"date-parts":[[2017,10,3]],"date-time":"2017-10-03T00:20:27Z","timestamp":1506990027000},"page":"3051-3062","source":"Crossref","is-referenced-by-count":9,"title":["NFAT1 Regulates Systemic Autoimmunity through the Modulation of a Dendritic Cell Property"],"prefix":"10.1093","volume":"199","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6398-6127","authenticated-orcid":false,"given":"Chang-Suk","family":"Chae","sequence":"first","affiliation":[{"name":"Academy of Immunology and Microbiology, Institute for Basic Science , Pohang 37673,","place":["Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gi-Cheon","family":"Kim","sequence":"additional","affiliation":[{"name":"Academy of Immunology and Microbiology, Institute for Basic Science , Pohang 37673,","place":["Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun Sil","family":"Park","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Gwangju Institute of Science and Technology , Gwangju 61005,","place":["Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7977-0408","authenticated-orcid":false,"given":"Choong-Gu","family":"Lee","sequence":"additional","affiliation":[{"name":"Academy of Immunology and Microbiology, Institute for Basic Science , Pohang 37673,","place":["Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ravi","family":"Verma","sequence":"additional","affiliation":[{"name":"Academy of Immunology and Microbiology, Institute for Basic Science , Pohang 37673,","place":["Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6577-5320","authenticated-orcid":false,"given":"Hagg-Lim","family":"Cho","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Gwangju Institute of Science and Technology , Gwangju 61005,","place":["Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang-Duk","family":"Jun","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Gwangju Institute of Science and Technology , Gwangju 61005,","place":["Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yung Joon","family":"Yoo","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Gwangju Institute of Science and Technology , Gwangju 61005,","place":["Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3173-1856","authenticated-orcid":false,"given":"Sin-Hyeog","family":"Im","sequence":"additional","affiliation":[{"name":"Academy of Immunology and Microbiology, Institute for Basic Science , Pohang 37673,","place":["Republic of Korea"]},{"name":"Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology , Pohang 37673,","place":["Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2017,11,1]]},"reference":[{"key":"2025030614511576500_r1","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1101\/gad.1102703","article-title":"Transcriptional regulation by calcium, calcineurin, and NFAT","volume":"17","author":"Hogan","year":"2003","journal-title":"Genes Dev."},{"key":"2025030614511576500_r2","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1038\/nri1632","article-title":"NFAT proteins: key regulators of T-cell development and function","volume":"5","author":"Macian","year":"2005","journal-title":"Nat. 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