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19.03.2020 | Original Research Paper | Ausgabe 5/2020

Inflammation Research 5/2020

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

Inflammation Research > Ausgabe 5/2020
Xiao-Hui Niu, Yun-Peng Xie, Song Yang, Yanchun Chen, Liang Xu, Ying Zhang, Yang Liu
Wichtige Hinweise
Communicated by John Di Battista.

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s00011-020-01330-4) contains supplementary material, which is available to authorized users.
Xiao-Hui Niu and Yun-Peng Xie contributed equally to this work.

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Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.



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.


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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