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Tarm1 may affect colitis by regulating macrophage M1 polarization in a mouse colitis model

Pediatric Research volume 98, pages 286–293 (2025)Cite this article

Abstract

Background

In this study, we aimed to explore the role of Tarm1 in juvenile mice with dextran sulfate sodium (DSS)-induced colitis and elucidate the mechanisms that affect intestinal barrier function.

Methods

A DSS-induced pediatric inflammatory bowel disease mouse model was established using 4-week-old juvenile mice. Disease activity index and histopathological damage scores were determined using hematoxylin and eosin (H&E) staining. Tarm1, F4/80, CD68, and CD86 levels were detected using qPCR, western blotting, and immunofluorescence. Trans epithelial electric resistance (TEER) was detected using the transwell assay.

Results

Results revealed that juvenile colitis mice fed 4% DSS drinking water had increased Tarm1 expression in the colon tissue, increased macrophage M1 polarization, higher expression of pro-inflammatory cytokines, and an impaired intestinal mucosal barrier, compared with the control group. Tarm1-knockdown RAW264.7 cells inhibited lipopolysaccharide (LPS)-induced M1 polarization and attenuated barrier damage in co-cultured intestinal epithelial cells.

Conclusion

Tarm1 expression was increased in colonic tissues of juvenile mice with colitis, and LPS-induced M1 polarization and intestinal barrier damage were attenuated in Tarm1-knockdown RAW264.7 cells. This suggests that attenuation of Tarm1 expression is a potential target for pediatric inflammatory bowel disease therapy.

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Fig. 1: Establishment of a mouse chemical colitis model.
Fig. 2: Elevated Tarm1 expression in the colon of DSS-induced colitis mice.
Fig. 3: Immunofluorescence of colonic Tarm1 and macrophages in the DSS and CON groups.
Fig. 4: High Tarm1 expression in M1 macrophages in the colon of DSS colitis mice.
Fig. 5: Relationship of Tarm1 to macrophage M1 polarization and its relationship to the intestinal barrier.

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Data availability

The authors confirm that the data supporting the findings of this study are available within the article.

References

  1. Jans, D. & Cleynen, I. The genetics of non-monogenic IBD. Hum. Genet. 142, 669–682 (2023).

    Article  PubMed  Google Scholar 

  2. Wang, X. Q. et al. Inflammatory bowel disease in Chinese children: a multicenter analysis over a decade from Shanghai. Inflamm. Bowel Dis. 19, 423–428 (2013).

    Article  PubMed  Google Scholar 

  3. Kudo, T. et al. Very early-onset inflammatory bowel disease in Japan: a nationwide survey. J. Gastroenterol. Hepatol. 36, 151–155 (2021).

    Article  CAS  PubMed  Google Scholar 

  4. Spalinger, M. R. et al. PTPN2 regulates interactions between macrophages and intestinal epithelial cells to promote intestinal barrier function. Gastroenterology 159, 1763–77 e14 (2020).

    Article  CAS  PubMed  Google Scholar 

  5. Na, Y. R., Stakenborg, M., Seok, S. H. & Matteoli, G. Macrophages in intestinal inflammation and resolution: a potential therapeutic target in IBD. Nat. Rev. Gastroenterol. Hepatol. 16, 531–543 (2019).

    Article  CAS  PubMed  Google Scholar 

  6. Gerner, R. R. et al. NAD metabolism fuels human and mouse intestinal inflammation. Gut 67, 1813–1823 (2018).

    Article  CAS  PubMed  Google Scholar 

  7. Bain, C. C. et al. Resident and pro-inflammatory macrophages in the colon represent alternative context-dependent fates of the same Ly6Chi monocyte precursors. Mucosal Immunol. 6, 498–510 (2013).

    Article  CAS  PubMed  Google Scholar 

  8. Delfini, M., Stakenborg, N., Viola, M. F. & Boeckxstaens, G. Macrophages in the gut: masters in multitasking. Immunity 55, 1530–1548 (2022).

    Article  CAS  PubMed  Google Scholar 

  9. Viola, M. F. & Boeckxstaens, G. Niche-specific functional heterogeneity of intestinal resident macrophages. Gut. 70, 1383–1395 (2021).

    Article  CAS  PubMed  Google Scholar 

  10. Castro-Dopico, T. et al. GM-CSF calibrates macrophage defense and wound healing programs during intestinal infection and inflammation. Cell Rep. 32, 107857 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Lissner, D. et al. Monocyte and M1 macrophage-induced barrier defect contributes to chronic intestinal inflammation in IBD. Inflamm. Bowel Dis. 21, 1297–1305 (2015).

    PubMed  Google Scholar 

  12. Zhou, X. et al. YAP aggravates inflammatory bowel disease by regulating M1/M2 macrophage polarization and gut microbial homeostasis. Cell Rep. 27, 1176–89 e5 (2019).

    Article  CAS  PubMed  Google Scholar 

  13. Pull, S. L., Doherty, J. M., Mills, J. C., Gordon, J. I. & Stappenbeck, T. S. Activated macrophages are an adaptive element of the colonic epithelial progenitor niche necessary for regenerative responses to injury. Proc. Natl Acad. Sci. USA 102, 99–104 (2005).

    Article  CAS  PubMed  Google Scholar 

  14. Guo, J., Zhang, Y. Y., Sun, M. & Xu, L. F. Therapeutic potential of curcumin in a rat model of dextran sulfate sodium-induced ulcerative colitis by regulating the balance of Treg/Th17 cells. Inflammation 45, 2163–2171 (2022).

    Article  CAS  PubMed  Google Scholar 

  15. Li, G. et al. Microbiota metabolite butyrate constrains neutrophil functions and ameliorates mucosal inflammation in inflammatory bowel disease. Gut Microbes 13, 1968257 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Guo, F. et al. Polyphenol Content of Green Pea (Pisum sativum L.) hull under in vitro digestion and effects of digestive products on anti-inflammatory activity and intestinal barrier in the Caco-2/Raw264.7 Coculture Model. J. Agric Food Chem. 70, 3477–3488 (2022).

    Article  CAS  PubMed  Google Scholar 

  17. Hegarty, L. M., Jones, G. R. & Bain, C. C. Macrophages in intestinal homeostasis and inflammatory bowel disease. Nat. Rev. Gastroenterol. Hepatol. 20, 538–553 (2023).

    Article  PubMed  Google Scholar 

  18. Hua, H. et al. Probiotic lactic acid bacteria alleviate pediatric IBD and remodel gut microbiota by modulating macrophage polarization and suppressing epithelial apoptosis. Front. Microbiol. 14, 1168924 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  19. Sommer, K. et al. Intestinal mucosal wound healing and barrier integrity in IBD-Crosstalk and trafficking of cellular players. Front. Med. 8, 643973 (2021).

    Article  Google Scholar 

  20. Al-Ghadban, S., Kaissi, S., Homaidan, F. R., Naim, H. Y. & El-Sabban, M. E. Cross-talk between intestinal epithelial cells and immune cells in inflammatory bowel disease. Sci. Rep. 6, 29783 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. De Sablet, T. et al. Cryptosporidium parvum increases intestinal permeability through interaction with epithelial cells and IL-1beta and TNFalpha released by inflammatory monocytes. Cell Microbiol. 18, 1871–1880 (2016).

    Article  PubMed  Google Scholar 

  22. Yabe, R. et al. TARM1 contributes to development of arthritis by activating dendritic cells through recognition of collagens. Nat. Commun. 12, 94 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Radjabova, V. et al. TARM1 is a novel leukocyte receptor complex-encoded ITAM receptor that costimulates proinflammatory cytokine secretion by macrophages and neutrophils. J. Immunol. 195, 3149–3159 (2015).

    Article  CAS  PubMed  Google Scholar 

  24. Li, X. et al. TARM-1 is critical for macrophage activation and Th1 response in mycobacterium tuberculosis infection. J. Immunol. 207, 234–243 (2021).

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was supported by the [Basic Research Projects of Liaoning Provincial Department of Education in 2022] under Grant [LJKMZ20221184] from Jing Guo, National Key Research and Development Program of China [2023YFC2706503] and 345 Talent Project from Lingfen Xu.

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Author notes

  1. These authors contributed equally: Kun Zhang, Lingfen Xu.

Authors and Affiliations

  1. Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, PR China

    Kun Zhang, Lingfen Xu & Jing Guo

Authors
  1. Kun Zhang
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  2. Lingfen Xu
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  3. Jing Guo
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Contributions

All authors contributed to the study conception and design. Author Kun Zhang had the primary responsibility for animal experiments, cell experiments, outcome assessment, preliminary data analysis and drafting the manuscript. Author Lingfen Xu revised the article critically for important intellectual content. Author Jing Guo as a communication author contributed to the writing of the manuscript and the overall guidance. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Jing Guo.

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The authors declare no competing interests.

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All authors read and approved the final manuscript.

Ethical approval

This study was approved by the Ethics Committee of the Affiliated Shengjing Hospital of the China Medical University (approval no. 2023PS203K; Shenyang, China).

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Zhang, K., Xu, L. & Guo, J. Tarm1 may affect colitis by regulating macrophage M1 polarization in a mouse colitis model. Pediatr Res 98, 286–293 (2025). https://doi.org/10.1038/s41390-024-03640-3

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