Extracellular adenosine induces hypersecretion of IL-17A by T-helper 17 cells through the adenosine A2a receptor

Tokano, Mieko; Matsushita, Sho; Takagi, Ryukichi; T, Yamamoto; Kawano, Masaaki

doi:10.1016/j.bbih.2022.100544

Cited by 6 publications

(1 citation statement)

References 79 publications

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“…Adenosine receptor A2A is also abundantly expressed in ILC3 and has been reported to be able to increase the production of Il-22 [44]. It was also reported to induce Il-17 secretion by Th17 cells [45]. These reports suggested that the adenosine content of RH, along with its other bioactive compounds, such as ergothioneine, arginine, BCAAs, and also SCFAs might contribute to its colitis-alleviating effect.…”

Section: Discussionmentioning

confidence: 98%

Investigation of Rhizopus oligosporus Metabolites in Fermented Wheat Bran and Its Bio Function in Alleviating Colitis in Mice Model

Agista,

Chien,

Koseki

et al. 2024

Metabolites

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Wheat bran (WB) is a low-value by-product of the wheat milling industry. Solid-state fermentation with Rhizopus oligosporus is performed to improve WB’s nutritional quality (RH). Twenty-five mice (11-week-old C57BL/6N male mice) were divided into three groups. The first group was fed a control diet (n = 8), the second group a 10% WB-supplemented diet (n = 8), and the last group had a 10% RH-supplemented diet (n = 9). The diet treatment was administered for 4 days before dextran sodium sulfate (DSS, 3% in drinking water) was administered for 9 days. RH supplementation prevented bodyweight loss and reduced the disease activity index in mice. An increase in the level of SCFAs in mouse intestines was detected post-RH supplementation, suggesting that SCFAs might have contributed to its anti-colitis effect. Metabolome analysis was conducted to explore other bioactive compounds in RH. R. oligosporus fermentation significantly increased the amounts of ergothioneine, arginine, branched-chain amino acids, and adenosine in wheat bran. All of these compounds are known to have antioxidant and anti-inflammatory capacities. These bioactive compounds might also have contributed to the RH’s ability to ameliorate DSS-induced colitis.

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Section: Discussionmentioning

confidence: 98%

Investigation of Rhizopus oligosporus Metabolites in Fermented Wheat Bran and Its Bio Function in Alleviating Colitis in Mice Model

Agista,

Chien,

Koseki

et al. 2024

Metabolites

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Adenosine A2B receptor activation regulates the balance between T helper 17 cells and regulatory T cells, and inhibits regulatory T cells exhaustion in experimental autoimmune myositis

Zhou,

Kang,

Yin

et al. 2024

J cachexia sarcopenia muscle

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BackgroundIdiopathic inflammatory myopathy (IIM) is a systemic autoimmune disease characterized by skeletal muscle involvement. This study aimed to investigate the role of adenosine receptor signalling pathways in the development of experimental autoimmune myositis (EAM).MethodsAn ecto‐5′‐nucleotidase (CD73) inhibitor, adenosine receptor agonists, a hypoxia‐inducible factor‐1α (HIF‐1α) inhibitor or a vehicle were administered to control and EAM mice. Murine splenic CD4+ or regulatory T cells (Tregs) were isolated using magnetic beads and subsequently stimulated with an adenosine A2B receptor agonist, a HIF‐1α inhibitor, or vehicle in vitro. In cross‐sectional studies, we collected 64 serum samples (69% female, 49 ± 9 years), 63 peripheral blood samples (70% female, 50 ± 11 years), and 34 skeletal muscle samples (71% female, 63 ± 6 years) from patients with IIM. Additionally, 35 serum samples and 30 peripheral blood samples were obtained from age‐ and sex‐matched healthy controls, and six quadriceps muscle samples were collected from patients with osteoarthritis to serve as the normal group.ResultsPatients with IIM exhibited increased CD73 [dermatomyositis (DM), polymyositis (PM): P < 0.01; immune‐mediated necrotizing myopathy (IMNM): P < 0.0001] and adenosine deaminase (ADA) expression (DM: P < 0.001; PM, IMNM: P < 0.0001) in the skeletal muscles, and serum ADA levels [56.7 (95% CI: 53.7, 58.7) vs. 198.8 (95% CI: 186.2, 237.3) ng/μL, P < 0.0001]. Intervention with a CD73 inhibitor exacerbated (P = 0.0461), whereas adenosine receptor agonists (A1: P = 0.0009; A2B: P < 0.0001; A3: P = 0.0001) and the HIF‐1α inhibitor (P = 0.0044) alleviated skeletal muscle injury in EAM mice. Elevated expression of programmed cell death protein‐1 (PD1: P = 0.0023) and T‐cell immunoglobulin and mucin‐domain containing‐3 (TIM3: P < 0.0001) in skeletal muscles of patients with IIM were correlated with creatine kinase levels (PD1, r = 0.7072, P < 0.0001; TIM3, r = 0.4808, P = 0.0046). PD1+CD4+ (r = 0.3243, P = 0.0115) and PD1+CD8+ (r = 0.3959, P = 0.0017) T cells were correlated with Myositis Disease Activity Assessment Visual Analogue Scale scores (muscle) in IIM. The exhausted Tregs were identified in the skeletal muscles of patients with IIM. Activation of the A2B adenosine receptor downregulated HIF‐1α (protein or mRNA level, P < 0.01), resulting in decreased T helper cell 17 (Th17) (13.58% vs. 5.43%, P = 0.0201) and phosphorylated‐signal transducer and activator of transcription 3 (p‐STAT3)+ Th17 (16.32% vs. 6.73%, P = 0.0029), decreased exhausted Tregs (PD1+ Tregs: 53.55% vs. 40.28%, P = 0.0005; TIM3+ Tregs: 3.93% vs. 3.11%, P = 0.0029), and increased Tregs (0.45% vs. 2.89%, P = 0.0006) in EAM mice.ConclusionsThe exhausted T cells may be pathogenic in IIM, and the activation of adenosine A2B receptor signalling pathway can regulate Th17/Treg balance and inhibit Tregs exhaustion, thereby slowing EAM disease progression.

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Adenosine A2AR in viral immune evasion and therapy: unveiling new avenues for treating COVID-19 and AIDS

Atif,

Alsrhani,

Naz

et al. 2024

Mol Biol Rep

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Extracellular adenosine induces hypersecretion of IL-17A by T-helper 17 cells through the adenosine A2a receptor

Cited by 6 publications

References 79 publications

Investigation of Rhizopus oligosporus Metabolites in Fermented Wheat Bran and Its Bio Function in Alleviating Colitis in Mice Model

Investigation of Rhizopus oligosporus Metabolites in Fermented Wheat Bran and Its Bio Function in Alleviating Colitis in Mice Model

Adenosine A2B receptor activation regulates the balance between T helper 17 cells and regulatory T cells, and inhibits regulatory T cells exhaustion in experimental autoimmune myositis

Adenosine A2AR in viral immune evasion and therapy: unveiling new avenues for treating COVID-19 and AIDS

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