{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T08:36:18Z","timestamp":1785832578828,"version":"3.56.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T00:00:00Z","timestamp":1676505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Cystic fibrosis (CF), especially CF lung disease, is characterized by chronic infection, immune dysfunction including impairment of regulatory T cells (Tregs) and an exaggerated inflammatory response. CF transmembrane conductance regulator (CFTR) modulators have shown to improve clinical outcomes in people with CF (PwCF) with a wide range of CFTR mutations. However, it remains unclear whether CFTR modulator therapy also affects CF-associated inflammation. We aimed to examine the effect of elexacaftor\/tezacaftor\/ivacaftor therapy on lymphocyte subsets and systemic cytokines in PwCF.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Peripheral blood mononuclear cells and plasma were collected before and at three and six months after the initiation of elexacaftor\/tezacaftor\/ivacaftor therapy; lymphocyte subsets and systemic cytokines were determined using flow cytometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Elexacaftor\/tezacaftor\/ivacaftor treatment was initiated in 77 PwCF and improved percent predicted FEV1 by 12.5 points (p&amp;lt;0.001) at 3 months. During elexacaftor\/tezacaftor\/ivacaftor therapy, percentages of Tregs were enhanced (+18.7%, p&amp;lt;0.001), with an increased proportion of Tregs expressing CD39 as a marker of stability (+14.4%, p&amp;lt;0.001). Treg enhancement was more pronounced in PwCF clearing Pseudomonas aeruginosa infection. Only minor, non-significant shifts were observed among Th1-, Th2- and Th17-expressing effector T helper cells. These results were stable at 3- and 6-month follow-up. Cytokine measurements showed a significant decrease in interleukin-6 levels during treatment with elexacaftor\/tezacaftor\/ivacaftor (\u201350.2%, p&amp;lt;0.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Treatment with elexacaftor\/tezacaftor\/ivacaftor was associated with an increased percentage of Tregs, especially in PwCF clearing Pseudomonas aeruginosa infection. Targeting Treg homeostasis is a therapeutic option for PwCF with persistent Treg impairment.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1107437","type":"journal-article","created":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T09:14:56Z","timestamp":1676538896000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":24,"title":["Regulatory T cell enhancement in adults with cystic fibrosis receiving Elexacaftor\/Tezacaftor\/Ivacaftor 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