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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Authors

DAĎOVÁ Petra MIKULOVÁ Antónia JAROUŠEK Radim CHORVÁTOVÁ Michaela ULDRIJAN Stjepan KUBALA Lukáš

Year of publication 2023
Type Article in Periodical
Magazine / Source International Immunopharmacology
MU Faculty or unit

Faculty of Science

Citation
Web https://www.sciencedirect.com/science/article/pii/S1567576923014923
Doi http://dx.doi.org/10.1016/j.intimp.2023.111166
Keywords DEPENDENT PROTEIN-KINASE; CYCLIC-AMP; GENETIC ARCHITECTURE; PDE4 INHIBITOR; RESPONSES; MEMORY; NAIVE; LYMPHOCYTES; EXPRESSION; MODULATORS
Description The adenylyl cyclase (AC) signaling pathway is suggested to be a key regulator of immune system functions. However, specific effects of cyclic adenosine mono -phosphate (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.
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