A mini-review: phosphodiesterases in charge to balance intracellular cAMP during T-cell activation
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A mini-review: phosphodiesterases in charge to balance intracellular cAMP during T-cell activation. / Bielenberg, Marie; Kurelic, Roberta; Frantz, Stefan; Nikolaev, Viacheslav O.
in: FRONT IMMUNOL, Jahrgang 15, 2024, S. 1365484.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Review › Forschung
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TY - JOUR
T1 - A mini-review: phosphodiesterases in charge to balance intracellular cAMP during T-cell activation
AU - Bielenberg, Marie
AU - Kurelic, Roberta
AU - Frantz, Stefan
AU - Nikolaev, Viacheslav O
N1 - Copyright © 2024 Bielenberg, Kurelic, Frantz and Nikolaev.
PY - 2024
Y1 - 2024
N2 - T-cell activation is a pivotal process of the adaptive immune response with 3',5'-cyclic adenosine monophosphate (cAMP) as a key regulator of T-cell activation and function. It governs crucial control over T-cell differentiation and production of pro-inflammatory cytokines, such as IFN-γ. Intriguingly, levels of intracellular cAMP differ between regulatory (Treg) and conventional T-cells (Tcon). During cell-cell contact, cAMP is transferred via gap junctions between these T-cell subsets to mediate the immunosuppressive function of Treg. Moreover, the activation of T-cells via CD3 and CD28 co-stimulation leads to a transient upregulation of cAMP. Elevated intracellular cAMP levels are balanced precisely by phosphodiesterases (PDEs), a family of enzymes that hydrolyze cyclic nucleotides. Various PDEs play distinct roles in regulating cAMP and cyclic guanosine monophosphate (cGMP) in T-cells. Research on PDEs has gained growing interest due to their therapeutic potential to manipulate T-cell responses. So far, PDE4 is the best-described PDE in T-cells and the first PDE that is currently targeted in clinical practice to treat autoimmune diseases. But also, other PDE families harbor additional therapeutic potential. PDE2A is a dual-substrate phosphodiesterase which is selectively upregulated in Tcon upon activation. In this Mini-Review, we will highlight the impact of cAMP regulation on T-cell activation and function and summarize recent findings on different PDEs regulating intracellular cAMP levels in T-cells.
AB - T-cell activation is a pivotal process of the adaptive immune response with 3',5'-cyclic adenosine monophosphate (cAMP) as a key regulator of T-cell activation and function. It governs crucial control over T-cell differentiation and production of pro-inflammatory cytokines, such as IFN-γ. Intriguingly, levels of intracellular cAMP differ between regulatory (Treg) and conventional T-cells (Tcon). During cell-cell contact, cAMP is transferred via gap junctions between these T-cell subsets to mediate the immunosuppressive function of Treg. Moreover, the activation of T-cells via CD3 and CD28 co-stimulation leads to a transient upregulation of cAMP. Elevated intracellular cAMP levels are balanced precisely by phosphodiesterases (PDEs), a family of enzymes that hydrolyze cyclic nucleotides. Various PDEs play distinct roles in regulating cAMP and cyclic guanosine monophosphate (cGMP) in T-cells. Research on PDEs has gained growing interest due to their therapeutic potential to manipulate T-cell responses. So far, PDE4 is the best-described PDE in T-cells and the first PDE that is currently targeted in clinical practice to treat autoimmune diseases. But also, other PDE families harbor additional therapeutic potential. PDE2A is a dual-substrate phosphodiesterase which is selectively upregulated in Tcon upon activation. In this Mini-Review, we will highlight the impact of cAMP regulation on T-cell activation and function and summarize recent findings on different PDEs regulating intracellular cAMP levels in T-cells.
KW - Phosphoric Diester Hydrolases
KW - Phosphodiesterase Inhibitors/therapeutic use
KW - Cyclic AMP
KW - T-Lymphocytes
KW - Diethylstilbestrol/analogs & derivatives
U2 - 10.3389/fimmu.2024.1365484
DO - 10.3389/fimmu.2024.1365484
M3 - SCORING: Review article
C2 - 38524120
VL - 15
SP - 1365484
JO - FRONT IMMUNOL
JF - FRONT IMMUNOL
SN - 1664-3224
ER -