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Toll-like receptor 3 signaling drives enteric glial cells against dextran sulfate sodium-induced colitis in mice

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Abstract

The activation of toll-like receptor 3 (TLR3) has been reported to attenuate astrocytes injury in central nervous system, but its effect on enteric glial cells (EGCs) remains unknown. Here, we confirmed that the residence of EGCs was regulated by TLR3 agonist (polyinosinic-polycytidylic acid, PIC) or TLR3/dsRNA complex inhibitor in dextran sulfate sodium (DSS)-induced mice. In vitro, TLR3 signaling prevented apoptosis in EGCs and drove the secretion of EGCs-derived glial cell line-derived neurotrophic factor, 15-hydroxyeicosatetraenoic acid and S-nitrosoglutathione. PIC preconditioning enhanced the protective effects of EGCs against the dysfunction of intestinal epithelial barrier and the development of colitis in DSS-induced mice. Interestingly, PIC stimulation also promoted the effects of EGCs on converting macrophages to an M2-like phenotype and regulating the levels of inflammatory cytokines, including IL-1β, TNF-α and IL-10, in DSS-induced mice. These findings imply that TLR3 signaling in EGCs may provide a potential target for the prevention and treatment of colitis.

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Data availability

Data are available from the corresponding author on reasonable request.

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Funding

This study was supported by the Xing Lin Scholar Scientific Research Fund Project from Chongqing Hospital of Traditional Chinese Medicine (No. YYZX2021051) and the Doctoral Special Scientific Research Fund Project from Science & Technology Commission of Chongqing (No. CSTB2022BSXM-JCX0073).

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Authors and Affiliations

  1. Department of Gastroenterology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China

    Jian Zeng, Qiong-Qiong Lu, Xiao-Long Du, Ling Yuan & Xiao-Jun Yang

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  1. Jian Zeng
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  2. Qiong-Qiong Lu
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  3. Xiao-Long Du
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  4. Ling Yuan
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  5. Xiao-Jun Yang
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Contributions

JZ designed the study, performed the experiments, analyzed as well as interpreted data, and prepared the manuscript; QQL, XLD and LY performed the experiments; XJY analyzed data and critically revised the manuscript. All authors have read and agreed to the final version of the manuscript.

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Correspondence to Jian Zeng.

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Zeng, J., Lu, QQ., Du, XL. et al. Toll-like receptor 3 signaling drives enteric glial cells against dextran sulfate sodium-induced colitis in mice. J Mol Histol 55, 201–210 (2024). https://doi.org/10.1007/s10735-024-10184-7

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  • DOI: https://doi.org/10.1007/s10735-024-10184-7

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