J 2023

A forskolin-mediated increase in cAMP promotes T helper cell differentiation into the Th1 and Th2 subsets rather than into the Th17 subset

DAĎOVÁ, Petra, Antónia MIKULOVÁ, Radim JAROUŠEK, Michaela CHORVÁTOVÁ, Stjepan ULDRIJAN et. al.

Basic information

Original name

A forskolin-mediated increase in cAMP promotes T helper cell differentiation into the Th1 and Th2 subsets rather than into the Th17 subset

Authors

DAĎOVÁ, Petra (203 Czech Republic, belonging to the institution), Antónia MIKULOVÁ (703 Slovakia, belonging to the institution), Radim JAROUŠEK (203 Czech Republic, belonging to the institution), Michaela CHORVÁTOVÁ (703 Slovakia, belonging to the institution), Stjepan ULDRIJAN (203 Czech Republic, belonging to the institution) and Lukáš KUBALA

Edition

International Immunopharmacology, Elsevier, 2023, 1567-5769

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

Netherlands

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 5.600 in 2022

RIV identification code

RIV/00216224:14310/23:00133100

Organization unit

Faculty of Science

UT WoS

001112358600001

Keywords in English

DEPENDENT PROTEIN-KINASE; CYCLIC-AMP; GENETIC ARCHITECTURE; PDE4 INHIBITOR; RESPONSES; MEMORY; NAIVE; LYMPHOCYTES; EXPRESSION; MODULATORS

Tags

International impact, Reviewed
Změněno: 12/3/2024 12:56, Mgr. Marie Šípková, DiS.

Abstract

V originále

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.

Links

EF16_025/0007381, research and development project
Name: Preklinická progrese nových organických sloučenin s cílenou biologickou aktivitou
MUNI/A/1393/2022, interní kód MU
Name: Biomedicínské vědy III
Investor: Masaryk University