{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:24:57Z","timestamp":1784697897751,"version":"3.55.0"},"reference-count":56,"publisher":"American Society for Clinical Investigation","issue":"16","license":[{"start":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T00:00:00Z","timestamp":1661126400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["ES025534,HL062410,HL102245,HL152756"],"award-info":[{"award-number":["ES025534,HL062410,HL102245,HL152756"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,22]]},"abstract":"<jats:p>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells drive the immunopathogenesis of chronic beryllium disease (CBD), and their recruitment to the lung heralds the onset of granulomatous inflammation. We have shown that CD4\n                    <jats:sup>+<\/jats:sup>\n                    Tregs control granuloma formation in an HLA-DP2 Tg model of CBD. In these mice, beryllium oxide (BeO) exposure resulted in the accumulation of 3 distinct CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell subsets in the lung, with the majority of tissue-resident memory cells expressing FoxP3. The amount of Be regulated the number of total and antigen-specific CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells and Tregs in the lungs of HLA-DP2 Tg mice. Depletion of Tregs increased the number of IFN-\u03b3\u2013producing CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells and enhanced lung injury, while mice treated with IL-2\/\u03b1IL-2 complexes had increased Tregs and reduced inflammation and Be-responsive T cells in the lung. BeO-experienced resident Tregs suppressed anti-CD3\u2013induced proliferation of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells in a contact-dependent manner. CTLA-4 and ICOS blockade, as well as the addition of LPS to BeO-exposed mice, increased the effector T cell (Teff)\/Treg ratio and enhanced lung injury. Collectively, these data show that the protective role of tissue-resident Tregs is dependent on quantity of Be exposure and is overcome by blocking immune regulatory molecules or additional environmental insults.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.156098","type":"journal-article","created":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T12:00:58Z","timestamp":1657627258000},"source":"Crossref","is-referenced-by-count":6,"title":["Protective role of tissue-resident Tregs in a murine model of beryllium-induced disease"],"prefix":"10.1172","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7928-5365","authenticated-orcid":true,"given":"Shaikh M.","family":"Atif","sequence":"first","affiliation":[{"name":"Department of Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas G.","family":"Mack","sequence":"additional","affiliation":[{"name":"Department of Medicine 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