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Adenosine A2A receptor signaling affects IL-21/IL-22 cytokines and GATA3/T-bet transcription factor expression in CD4+ T cells from a BTBR T+ Itpr3tf/J mouse model of autism.
J Neuroimmunol 2017; 311:59-67JN

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.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Electronic address: fashaikh@ksu.edu.sa.Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; Department of Pharmacology and Toxicology, College of Pharmacy, Al-Azhar University, Cairo, Egypt.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28807491

Citation

Ahmad, Sheikh F., et al. "Adenosine A2A Receptor Signaling Affects IL-21/IL-22 Cytokines and GATA3/T-bet Transcription Factor Expression in CD4+ T Cells From a BTBR T+ Itpr3tf/J Mouse Model of Autism." Journal of Neuroimmunology, vol. 311, 2017, pp. 59-67.
Ahmad SF, Ansari MA, Nadeem A, et al. Adenosine A2A receptor signaling affects IL-21/IL-22 cytokines and GATA3/T-bet transcription factor expression in CD4+ T cells from a BTBR T+ Itpr3tf/J mouse model of autism. J Neuroimmunol. 2017;311:59-67.
Ahmad, S. F., Ansari, M. A., Nadeem, A., Bakheet, S. A., Almutairi, M. M., & Attia, S. M. (2017). Adenosine A2A receptor signaling affects IL-21/IL-22 cytokines and GATA3/T-bet transcription factor expression in CD4+ T cells from a BTBR T+ Itpr3tf/J mouse model of autism. Journal of Neuroimmunology, 311, pp. 59-67. doi:10.1016/j.jneuroim.2017.08.002.
Ahmad SF, et al. Adenosine A2A Receptor Signaling Affects IL-21/IL-22 Cytokines and GATA3/T-bet Transcription Factor Expression in CD4+ T Cells From a BTBR T+ Itpr3tf/J Mouse Model of Autism. J Neuroimmunol. 2017 10 15;311:59-67. PubMed PMID: 28807491.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Adenosine A2A receptor signaling affects IL-21/IL-22 cytokines and GATA3/T-bet transcription factor expression in CD4+ T cells from a BTBR T+ Itpr3tf/J mouse model of autism. AU - Ahmad,Sheikh F, AU - Ansari,Mushtaq A, AU - Nadeem,Ahmed, AU - Bakheet,Saleh A, AU - Almutairi,Mashal M, AU - Attia,Sabry M, Y1 - 2017/08/09/ PY - 2017/06/08/received PY - 2017/07/22/revised PY - 2017/08/09/accepted PY - 2017/8/16/pubmed PY - 2017/9/28/medline PY - 2017/8/16/entrez KW - Adenosine A2A receptor (A2AR) KW - Autism KW - BTBR T(+) Itpr3tf/J (BTBR) KW - Brain KW - C57BL/6 (B6) KW - CD152 (CTLA-4) KW - Cytokines KW - Spleen SP - 59 EP - 67 JF - Journal of neuroimmunology JO - J. Neuroimmunol. VL - 311 N2 - 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. SN - 1872-8421 UR - https://www.unboundmedicine.com/medline/citation/28807491/Adenosine_A2A_receptor_signaling_affects_IL_21/IL_22_cytokines_and_GATA3/T_bet_transcription_factor_expression_in_CD4+_T_cells_from_a_BTBR_T+_Itpr3tf/J_mouse_model_of_autism_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0165-5728(17)30253-9 DB - PRIME DP - Unbound Medicine ER -