Ablation of CD226 on CD4+ T cells modulates asthma progress associated with altered IL-10 response and gut microbiota.

Abstract

To investigate the role of the costimulatory molecule CD226 in asthma pathogenesis, we produced a CD4+ T-cell-specific CD226 knockout mice model (Cd226ΔCD4) and induced airway allergic inflammation by administering ovalbumin (OVA). Our results revealed alleviated lung inflammation, decreased levels of OVA-specific IgE, and increased levels of IL-10 in the serum of Cd226ΔCD4 mice (P < 0.05). Moreover, IL-10 levels in CD4+ T cells were significantly elevated in the mediastinal lymph node, spleen, and Peyer's patches in the Cd226ΔCD4 mice compared with those in controls (P < 0.05 to P < 0.01). Notably, there was a significantly higher IL-10 mRNA levels in the large intestine of the mice (P < 0.05). The protective effect of CD226 deficiency is also associated with the accumulation of gut TCRγδ+ intraepithelial lymphocytes and reversion of the gut microbiome dysbiosis. The Bacteroidetes-to-Firmicutes ratio and the abundance of Akkermansia increased in the absence of CD226 after OVA treatment. Our data reveal the synchronous changes in the lung and intestine in OVA-treated CD226-knockout mice, supporting the gut-lung axis concept and providing evidence for novel therapeutic approaches for asthma.

• Authors: Yang Xie, Yuan Zhang, Tingting Wang, Yitian Liu, Jingchang Ma, Shuwen Wu, Chujun Duan, Wei Qiao, Kun Cheng, Lianjun Lu, Ran Zhuang, Ka Bian
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 118 Pg. 110051 (May 2023) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 36989896 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 Elsevier B.V. All rights reserved.

Chemical References

• Interleukin-10
• Ovalbumin
• Cytokines

Topics

• Mice
• Animals
• Gastrointestinal Microbiome
• Interleukin-10 (genetics, therapeutic use)
• Asthma (drug therapy)
• Mice, Knockout
• CD4-Positive T-Lymphocytes
• Ovalbumin (therapeutic use)
• Mice, Inbred BALB C
• Disease Models, Animal
• Cytokines (therapeutic use)
• Bronchoalveolar Lavage Fluid