Abstract
Autism is a complex heterogeneous neurodevelopmental disorder; previous studies have identified altered immune responses among individuals diagnosed with autism. An imbalance in the production of pro- and anti-inflammatory cytokines and transcription factors plays a role in neurodevelopmental behavioral and autism disorders. BTBR T+ Itpr3tf/J (BTBR) mice are used as a model for autism, as they exhibit social deficits, communication deficits, and repetitive behaviors compared with C57BL/6J (B6) mice. The adenosine A2A receptor (A2AR) appears to be a potential target for the improvement of behavioral, inflammatory, immune, and neurological disorders. We investigated the effects of the A2AR antagonist SCH 5826 (SCH) and agonist CGS 21680 (CGS) on IL-21, IL-22, T-bet, T-box transcription factor (T-bet), GATA3 (GATA Binding Protein 3), and CD152 (CTLA-4) expression in BTBR mice. Our results showed that BTBR mice treated with SCH had increased CD4+IL-21+, CD4+IL-22+, CD4+GATA3+, and CD4+T-bet+ and decreased CD4+CTLA-4+ expression in spleen cells compared with BTBR control mice. Moreover, CGS efficiently decreased CD4+IL-21+, CD4+IL-22+, CD4+GATA3+, and CD4+T-bet+ and increased CD4+CTLA-4 production in spleen cells compared with SCH-treated and BTBR control mice. Additionally, SCH treatment significantly increased the mRNA and protein expression levels of IL-21, IL-22, GATA3, and T-bet in brain tissue compared with CGS-treated and BTBR control mice. The augmented levels of IL-21/IL-22 and GATA3/T-bet could be due to altered A2AR signaling. Our results indicate that A2AR agonists may represent a new class of compounds that can be developed for use in the treatment of autistic and neuroimmune dysfunctions.
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•Effect of A2AR expression on IL-21/IL-22 and GAT-3/T-bet was investigated in BTBR mice.•An A2AR antagonist promotes IL-21/IL-22 and GAT-3/T-bet expression.•An A2AR agonist decreases IL-21/IL-22 and GAT-3/T-bet expression.•A2AR modulates CTLA-4 production in BTBR mice.•An A2AR agonist might serve as a therapeutic target in autism.