TY - JOUR
T1 - Adenosine A2B receptor antagonist suppresses differentiation to regulatory T cells without suppressing activation of T cells
AU - Nakatsukasa, Hiroko
AU - Tsukimoto, Mitsutoshi
AU - Harada, Hitoshi
AU - Kojima, Shuji
N1 - Funding Information:
Parts of this work were supported by Grant-in-Aid for Scientific Research (C) (to S.K.), for Young Scientists (B) (to M.T.), and for JSPS Fellows (to H.N.) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan .
PY - 2011/5/27
Y1 - 2011/5/27
N2 - Extracellular adenosine activates P1 receptors (A1, A2A, A2B, A3) 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 A1 and A2B receptors suppressed the expression of Foxp3, a specific marker of Treg, and the production of IL-10, suggesting the involvement of A1 and A2B 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 A1 antagonist, but not A2B antagonist, suppressed T cell activation. We conclude that A1 and A2B receptors are both involved in differentiation to Treg, but through different mechanisms. Since A2B antagonist blocked differentiation to Treg without suppressing T cell activation, it is possible that blockade of A2B receptor would facilitate tumor immunity.
AB - Extracellular adenosine activates P1 receptors (A1, A2A, A2B, A3) 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 A1 and A2B receptors suppressed the expression of Foxp3, a specific marker of Treg, and the production of IL-10, suggesting the involvement of A1 and A2B 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 A1 antagonist, but not A2B antagonist, suppressed T cell activation. We conclude that A1 and A2B receptors are both involved in differentiation to Treg, but through different mechanisms. Since A2B antagonist blocked differentiation to Treg without suppressing T cell activation, it is possible that blockade of A2B receptor would facilitate tumor immunity.
KW - A1 receptor
KW - A2B receptor
KW - Adenosine
KW - Foxp3
KW - Regulatory T cell
KW - T cell differentiation
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U2 - 10.1016/j.bbrc.2011.04.125
DO - 10.1016/j.bbrc.2011.04.125
M3 - Article
C2 - 21557932
AN - SCOPUS:79956191026
SN - 0006-291X
VL - 409
SP - 114
EP - 119
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -