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A forskolin-mediated increase in cAMP promotes T helper cell differentiation into the Th1 and Th2 subsets rather than into the Th17 subset
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SYSNO ASEP 0583605 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title A forskolin-mediated increase in cAMP promotes T helper cell differentiation into the Th1 and Th2 subsets rather than into the Th17 subset Author(s) Daďová, Petra (BFU-R) ORCID
Mikulová, Antónia (BFU-R)
Jaroušek, Radim (BFU-R)
Chorvátová, Michaela (BFU-R)
Uldrijan, S. (CZ)
Kubala, Lukáš (BFU-R) RID, ORCIDNumber of authors 6 Article number 111166 Source Title International Immunopharmacology. - : Elsevier - ISSN 1567-5769
Roč. 125, DEC 2023 (2023)Number of pages 15 s. Publication form Online - E Language eng - English Country NL - Netherlands Keywords dependent protein-kinase ; cyclic-amp ; genetic architecture ; pde4 inhibitor ; responses ; memory ; naive ; lymphocytes ; expression ; modulators Subject RIV EC - Immunology OECD category Immunology Method of publishing Open access Institutional support BFU-R - RVO:68081707 UT WOS 001112358600001 EID SCOPUS 85176617007 DOI 10.1016/j.intimp.2023.111166 Annotation The adenylyl cyclase (AC) signaling pathway is suggested to be a key regulator of immune system functions. However, specific effects of cyclic adenosine monophosphate (cAMP) on T helper (Th) cell differentiation and functions are unclear. The involvement of cAMP in the Th cell differentiation program, in particular the development of Th1, Th2, and Th17 subsets, was evaluated employing forskolin (FSK), a labdane diterpene well known as an AC activator. FSK mediated an elevation in Th1-specific markers reinforcing the Th1 cell phenotype. The Th2 differentiation was supported by FSK, though cell metabolism was negatively affected. In contrast, the Th17 immunophenotype was severely suppressed leading to the highly specific upregulation of CXCL13. The causality between FSK-elicited cAMP production and the observed reinforcement of Th2 differentiation was established by using AC inhibitor 2 ',5 '-dideoxyadenosine, which reverted the FSK effects. Overall, an FSK-mediated cAMP increase affects Th1, Th2 and Th17 differentiation and can contribute to the identification of novel therapeutic targets for the treatment of Th cell-related pathological processes. Workplace Institute of Biophysics Contact Jana Poláková, polakova@ibp.cz, Tel.: 541 517 244 Year of Publishing 2024 Electronic address https://www.sciencedirect.com/science/article/pii/S1567576923014923?via%3Dihub
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