Distinct metabolism of cyclic adenosine monophosphate in regulatory and helper CD4+ T cells

• Verfasst von: Bazhin, Alexandr V. [VerfasserIn]
• Verfasst von: Kahnert, Sarah [VerfasserIn]
• Verfasst von: Kimpfler, Silvia [VerfasserIn]
• Verfasst von: Schadendorf, Dirk [VerfasserIn]
• Verfasst von: Umansky, Viktor [VerfasserIn]
• Titel: Distinct metabolism of cyclic adenosine monophosphate in regulatory and helper CD4+ T cells
• Verf.angabe: Alexandr V. Bazhin, Sarah Kahnert, Silvia Kimpfler, Dirk Schadendorf, Viktor Umansky
• Jahr: 2010
• Umfang: 7 S.
• Fussnoten: Im Titel ist das Pluszeichen hochgestellt ; Available online 24 November 2009 ; Gesehen am 16.12.2022
• Titel Quelle: Enthalten in: Molecular immunology
• Ort Quelle: Amsterdam [u.a.] : Elsevier, 1979
• Jahr Quelle: 2010
• Band/Heft Quelle: 47(2010), 4, Seite 678-684
• ISSN Quelle: 1872-9142
• DOI: doi:10.1016/j.molimm.2009.10.032
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Adenylyl cyclases
• Sach-SW: Cyclic adenosine monophosphate
• Sach-SW: Interleukin-2
• Sach-SW: Phosphodiesterases
• Sach-SW: Regulatory T cells
• K10plus-PPN: 1827667486

Abstract

Regulatory T cells (Treg) are crucial for the suppression of antigen-specific immune responses by activated conventional T cells (Tcon). It has been recently reported that this suppression is mediated by cyclic adenosine monophosphate (cAMP) transported from Treg to Tcon via gap junctions. However, the underlying biochemical mechanisms of cAMP accumulation in activated Treg are still unclear. Here we reported that although non-activated murine Treg and Tcon displayed similar intracellular cAMP amounts, both subpopulations showed distinct expression of enzymes regulating cAMP metabolism. Thus, in Treg, activities of both anabolic (adenylyl cyclase, AC) and catabolic (phosphodiesterase, PDE) enzymes were lower than in Tcon. Furthermore, we demonstrated for the first time the expression of the PDE11 protein in murine Treg and Tcon. Treg activation by IL-2 induced a strong AC7 activation and cAMP accumulation in Treg. In contrast, Tcon showed a significant decrease in the AC7 activity and cAMP amounts under these conditions. Our data suggest that the mechanism of cAMP accumulation in stimulated Treg involves the AC7 activation and provide new insight into the modulation of Treg activities via AC inhibition or stimulation in various pathological processes like tumor and autoimmune diseases.