IL-15 Prevents Renal Fibrosis by Inhibiting Collagen Synthesis: A New Pathway in Chronic Kidney Disease?

Devocelle, Aurore; Lecru, Lola; Ferlicot, Sophie; Bessede, Thomas; Candelier, Jean-Jacques; Giron-Michel, Julien; François, Hélène

doi:10.3390/ijms222111698

Open AccessArticle

IL-15 Prevents Renal Fibrosis by Inhibiting Collagen Synthesis: A New Pathway in Chronic Kidney Disease?

by

Aurore Devocelle

^1,2,

Lola Lecru

^1,2,

Sophie Ferlicot

³,

Thomas Bessede

⁴,

Jean-Jacques Candelier

^1,2,

Julien Giron-Michel

^1,2,*,†

and

Hélène François

^5,6,*,†

¹

INSERM UMR-S-MD 1197/Ministry of the Armed Forces, Biomedical Research Institute of the Armed Forces (IRBA), Paul-Brousse Hospital Villejuif and CTSA Clamart, 94807 Villejuif, France

²

Orsay-Vallée Campus, Paris-Saclay University, 91190 Gif-sur-Yvette, France

³

Service d’Anatomopathologie, Hôpital Bicêtre, AP-HP, 94270 Le Kremlin-Bicêtre, France

⁴

Service d’Urologie, Hôpital Bicêtre, AP-HP, 94270 Le Kremlin-Bicêtre, France

⁵

INSERM UMR_S1155, Tenon Hospital, 75020 Paris, France

⁶

Soins Intensifs Néphrologiques et Rein Aigu (SINRA), Hôpital Tenon, AP-HP, Sorbonne University, 75020 Paris, France

^*

Authors to whom correspondence should be addressed.

^†

These authors contribute equally to this work.

Int. J. Mol. Sci. 2021, 22(21), 11698; https://doi.org/10.3390/ijms222111698

Submission received: 24 September 2021 / Revised: 21 October 2021 / Accepted: 26 October 2021 / Published: 28 October 2021

(This article belongs to the Special Issue Molecular Mechanisms and Therapies for Kidney Diseases)

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Abstract

Chronic kidney disease (CKD), secondary to renal fibrogenesis, is a public health burden. The activation of interstitial myofibroblasts and excessive production of extracellular matrix (ECM) proteins are major events leading to end-stage kidney disease. Recently, interleukin-15 (IL-15) has been implicated in fibrosis protection in several organs, with little evidence in the kidney. Since endogenous IL-15 expression decreased in nephrectomized human allografts evolving toward fibrosis and kidneys in the unilateral ureteral obstruction (UUO) model, we explored IL-15’s renoprotective role by pharmologically delivering IL-15 coupled or not with its soluble receptor IL-15Rα. Despite the lack of effects on myofibroblast accumulation, both IL-15 treatments prevented tubulointerstitial fibrosis (TIF) in UUO as characterized by reduced collagen and fibronectin deposition. Moreover, IL-15 treatments inhibited collagen and fibronectin secretion by transforming growth factor-β (TGF-β)-treated primary myofibroblast cultures, demonstrating that the antifibrotic effect of IL-15 in UUO acts, in part, through a direct inhibition of ECM synthesis by myofibroblasts. In addition, IL-15 treatments resulted in decreased expression of monocyte chemoattractant protein 1 (MCP-1) and subsequent macrophage infiltration in UUO. Taken together, our study highlights a major role of IL-15 on myofibroblasts and macrophages, two main effector cells in renal fibrosis, demonstrating that IL-15 may represent a new therapeutic option for CKD.

Keywords: chronic kidney disease; fibrosis; unilateral ureteral obstruction; interleukin-15; myofibroblasts; extracellular matrix

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MDPI and ACS Style

Devocelle, A.; Lecru, L.; Ferlicot, S.; Bessede, T.; Candelier, J.-J.; Giron-Michel, J.; François, H. IL-15 Prevents Renal Fibrosis by Inhibiting Collagen Synthesis: A New Pathway in Chronic Kidney Disease? Int. J. Mol. Sci. 2021, 22, 11698. https://doi.org/10.3390/ijms222111698

AMA Style

Devocelle A, Lecru L, Ferlicot S, Bessede T, Candelier J-J, Giron-Michel J, François H. IL-15 Prevents Renal Fibrosis by Inhibiting Collagen Synthesis: A New Pathway in Chronic Kidney Disease? International Journal of Molecular Sciences. 2021; 22(21):11698. https://doi.org/10.3390/ijms222111698

Chicago/Turabian Style

Devocelle, Aurore, Lola Lecru, Sophie Ferlicot, Thomas Bessede, Jean-Jacques Candelier, Julien Giron-Michel, and Hélène François. 2021. "IL-15 Prevents Renal Fibrosis by Inhibiting Collagen Synthesis: A New Pathway in Chronic Kidney Disease?" International Journal of Molecular Sciences 22, no. 21: 11698. https://doi.org/10.3390/ijms222111698

APA Style

Devocelle, A., Lecru, L., Ferlicot, S., Bessede, T., Candelier, J.-J., Giron-Michel, J., & François, H. (2021). IL-15 Prevents Renal Fibrosis by Inhibiting Collagen Synthesis: A New Pathway in Chronic Kidney Disease? International Journal of Molecular Sciences, 22(21), 11698. https://doi.org/10.3390/ijms222111698

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IL-15 Prevents Renal Fibrosis by Inhibiting Collagen Synthesis: A New Pathway in Chronic Kidney Disease?

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