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IL-18/IL-18R1 promotes circulating fibrocyte differentiation in the aging population

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Abstract

Background

Fibrosis in multiple organs increases with age. Circulating fibrocytes are bone-marrow-derived mesenchymal progenitors that contribute to heart, lung, and kidney fibrosis under the diseased conditions. Whether circulating fibrocytes contribute to aging-related fibrosis is very limited.

Methods and results

We measured the proportion and differentiation of circulating fibrocytes (CD45+/CD34+/collagen I+) from elders (n = 12) and adults (n = 12) using flow cytometry. Differentiated fibrocytes in the culture dishes were isolated and microarray was performed. The percentage of circulating fibrocytes in elders (1.95 ± 0.43%) was comparable to that in the adults (1.71 ± 0.38%). Cultured fibrocytes displayed enhanced potential of differentiation in the elder group (67.91 ± 5.88%) vs the adult group (44.03 ± 7.98%). In addition, expression of fibroblast activation markers and cell migratory ability were also increased in differentiated fibrocytes from elders. Microarray analysis revealed that differentiated fibrocytes from elders expressed high level of interleukin-18 (IL-18) receptor 1 (IL-18R1). Furthermore, we found IL-18 was elevated in the plasma of elders and IL-18/IL-18R1 was shown to promote fibrocyte differentiation.

Conclusion

Circulating fibrocytes from elders had an enhanced capacity to differentiate into myofibroblasts, and might contribute to age-dependent fibrosis. Age-dependent increment of differentiation at least in part arose from their enhanced expression of IL-18R1. Inhibiting fibrocyte differentiation might be useful as an adjuvant treatment to delay the fibrosis process in aging population.

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Acknowledgements

Yang Liu was supported by grants from Scientific Research Project of Education Department of Liaoning Province (LZ2019017). Ying Zhang was supported by grants from Scientific Research Project of Education Department of Liaoning Province (LZ2019021). Xiao-Hui Niu was supported by Clinical Medical Science and Technology Development Fund of Jiangsu University (JLY20180073).

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Author notes

  1. Xiao-Hui Niu and Yun-Peng Xie contributed equally to this work.

Authors and Affiliations

  1. Institute of Cardiovascular Diseases, The First Affiliated Hospital of Dalian Medical University, No 222, Zhongshan Rd, Dalian, China

    Xiao-Hui Niu, Yun-Peng Xie & Yang Liu

  2. Yixing People’s Hospital, The Affiliated Hospital of Jiangsu University, Yixing, China

    Xiao-Hui Niu, Song Yang, Yanchun Chen & Liang Xu

  3. Department of Cardiology, the First Affiliated Hospital of Dalian Medical University, No 222, Zhongshan Rd, Dalian, China

    Xiao-Hui Niu & Ying Zhang

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  1. Xiao-Hui Niu
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Contributions

YL and YZ designed the research, wrote the paper, and analyzed the data. XN and YX conducted experiments. SY, YC, and LX analyzed the data and contributed to revise the paper. All authors critically reviewed the manuscript for important intellectual content and approved the final version.

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Correspondence to Ying Zhang or Yang Liu.

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Communicated by John Di Battista.

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Niu, XH., Xie, YP., Yang, S. et al. IL-18/IL-18R1 promotes circulating fibrocyte differentiation in the aging population. Inflamm. Res. 69, 497–507 (2020). https://doi.org/10.1007/s00011-020-01330-4

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  • DOI: https://doi.org/10.1007/s00011-020-01330-4

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