title: Adenosine A2B receptor antagonist suppresses differentiation to regulatory T cells without suppressing activation of T cells.
abstract: Extracellular adenosine activates P1 receptors (A(1), A(2A), A(2B), A(3)) on cellular membranes. Here, we investigated the involvement of P1 receptor-mediated signaling in differentiation to regulatory T cells (Treg). Treg were induced in vitro by incubating isolated CD4(+)CD62L(+) naïve murine T cells under Treg-skewing conditions. Antagonists of A(1) and A(2B) receptors suppressed the expression of Foxp3, a specific marker of Treg, and the production of IL-10, suggesting the involvement of A(1) and A(2B) receptors in differentiation to Treg. We also investigated the effect of these antagonists on T cell activation, which is essential for differentiation to Treg, and found that A(1) antagonist, but not A(2B) antagonist, suppressed T cell activation. We conclude that A(1) and A(2B) receptors are both involved in differentiation to Treg, but through different mechanisms. Since A(2B) antagonist blocked differentiation to Treg without suppressing T cell activation, it is possible that blockade of A(2B) receptor would facilitate tumor immunity.
authors.affiliation: Department of Radiation Biosciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Yamazaki, Noda-shi, Chiba, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nakatsukasa
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Tsukimoto
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Harada
authors.forename: Shuji
authors.initials: S
authors.lastname: Kojima
mesh_terms: D058916:Adenosine A1 Receptor Antagonists / Q000494:pharmacology; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation; D051858:Forkhead Transcription Factors; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000276:immunology; D043682:Receptor, Adenosine A1 / Q000502:physiology*; D043704:Receptor, Adenosine A2B / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D043682:Receptor, Adenosine A1; D043704:Receptor, Adenosine A2B