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PI3K\/Akt signaling, critical for maintaining Treg's homeostasis, is aberrantly activated in sarcoidosis patients. Here we tested the role of the PI3K inhibitors, LY294002 and BKM120, in immune modulation in experimental pulmonary sarcoidosis, concerning Th1\/Th17\/Treg immune profile detected by fluorescence\u2010activated cell sorting analysis or quantitative polymerase chain reaction, as well as the effect on Treg's suppressive functions. Our investigation showed abnormal activation of PI3K\/Akt signaling both in lung and Treg in pulmonary sarcoidosis, along with decreased frequency and damaged function of Treg. Blockage of PI3K suppressed this signaling in Treg, rebalanced Th1\/Treg, inhibited the production of inflammatory cytokines, and enhanced Treg's function. These results demonstrate the key role of the PI3K\/Akt signaling in regulating Th1\/Th2 rebalances and indicates that PI3K\/Akt signaling is critical for the optimal Treg responses in pulmonary sarcoidosis. Thus, PI3K inhibitors have potential for therapeutic translation, and can be candidate for add\u2010on drugs to treat pulmonary sarcoidosis.<\/jats:p>","DOI":"10.1002\/jcp.28589","type":"journal-article","created":{"date-parts":[[2019,4,4]],"date-time":"2019-04-04T01:07:31Z","timestamp":1554340051000},"page":"19911-19920","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Phosphoinositide 3\u2010kinase\/protein kinase B inhibition restores regulatory T cell's function in pulmonary sarcoidosis"],"prefix":"10.1002","volume":"234","author":[{"given":"Bin","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Basic Medicine Center of Translational Medicine, Jiangsu Key Laboratory of Molecular Medicine, Nanjing University Medical School Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of 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