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Using Lyn-deficient mice, we show that overproduction of BAFF by hyperactive myeloid cells contributes to inflammation and autoimmunity in part by acting directly on T cells to induce the release of IFN-\u03b3. Genetic deletion of IFN-\u03b3 or reduction of BAFF activity, achieved by either reducing myeloid cell hyperproduction or by treating with an anti-BAFF monoclonal antibody, reduced disease development in lyn\u2212\/\u2212 mice. The increased production of IFN-\u03b3 in lyn\u2212\/\u2212 mice feeds back on the myeloid cells to further stimulate BAFF release. Expression of BAFF receptor on T cells was required for their full activation and IFN-\u03b3 release. Overall, our data suggest that the reciprocal production of BAFF and IFN-\u03b3 establishes an inflammatory loop between myeloid cells and T cells that exacerbates autoimmunity in this model. Our findings uncover an important pathological role of BAFF in autoimmune disorders.<\/jats:p>","DOI":"10.1084\/jem.20100086","type":"journal-article","created":{"date-parts":[[2010,7,12]],"date-time":"2010-07-12T23:00:12Z","timestamp":1278975612000},"page":"1757-1773","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":109,"title":["Myeloid cells, BAFF, and IFN-\u03b3 establish an inflammatory loop that exacerbates autoimmunity in Lyn-deficient mice"],"prefix":"10.1084","volume":"207","author":[{"given":"Patrizia","family":"Scapini","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine 1 and 2"},{"name":"Department of Microbiology\/Immunology, University of California, San Francisco, San Francisco, CA 94143 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongmei","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine 1 and 2"},{"name":"Department of Microbiology\/Immunology, University of California, San Francisco, San Francisco, CA 94143 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Liang","family":"Chu","sequence":"additional","affiliation":[{"name":"Immunology Research Center, National Health Research Institutes, Miaoli County 350, Taiwan 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thi-Sau","family":"Migone","sequence":"additional","affiliation":[{"name":"Human Genome Sciences, Inc., Rockville, MD 20850 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony L.","family":"DeFranco","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine 1 and 2"},{"name":"Department of Microbiology\/Immunology, University of California, San Francisco, San Francisco, CA 94143 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco A.","family":"Cassatella","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section of General Pathology, University of Verona, 37134 Verona, Italy 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clifford A.","family":"Lowell","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine 1 and 2"},{"name":"Department of Microbiology\/Immunology, University of California, San Francisco, San Francisco, CA 94143 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2010,7,12]]},"reference":[{"key":"2023072522123389100_bib1","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1097\/01.bor.0000169361.23325.1e","article-title":"New insights from murine lupus: disassociation of autoimmunity and end organ damage and the role of T cells","volume":"17","author":"Bagavant","year":"2005","journal-title":"Curr. 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