The role of Interleukin 1 receptor antagonist in mesenchymal stem cell-based tissue repair and regeneration.

Harrell, Carl Randall; Markovic, Bojana Simovic; Fellabaum, Crissy; Arsenijevic, Nebojsa; Djonov, Valentin; Volarevic, Vladislav (2020). The role of Interleukin 1 receptor antagonist in mesenchymal stem cell-based tissue repair and regeneration. BioFactors, 46(2), pp. 263-275. Wiley 10.1002/biof.1587

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Interleukin (IL)-1 receptor antagonist (IL-1Ra), a naturally occurring antagonist of IL-1α/IL-1β signaling pathways, has been attributed to the immunosuppressive effects of mesenchymal stem cells (MSCs). MSCs, in IL-1Ra-dependent manner, suppressed production of IL-1β in dermal macrophages, induced their polarization in anti-inflammatory M2 phenotype, attenuated antigen-presenting properties of dendritic cells (DCs), and promoted expansion of immunosuppressive T regulatory cells in the skin, which resulted in enhanced repair of the nonhealing wounds. Reduced activation of inflammasome and suppressed production of IL-1β in macrophages were mainly responsible for beneficial effects of MSC-derived IL-1Ra in alleviation of acute lung injury, dry eye syndrome, and corneal injury. Through the production of IL-1Ra, MSCs reduced migration of DCs to the draining lymph nodes and attenuated generation of inflammatory Th1 and Th17 cells that resulted in alleviation of fulminant hepatitis and rheumatoid arthritis. MSCs, in IL-1Ra-dependent manner, reduced liver fibrosis by suppressing production of Type I collagen in hepatic stellate cells. IL-1Ra was, at least partially, responsible for enhanced proliferation of hepatocytes and chondrocytes in MSC-treated animals with partial hepatectomy and osteoarthritis. Despite of these beneficial effects, IL-1Ra-dependent inhibition of IL-1α/IL-1β-signaling significantly increased risk of infections. Therefore, future experimental and clinical studies should delineate potential side effects of MSC-derived IL-1Ra before IL-1Ra-overexpressing MSCs could be used as a potentially new therapeutic agent for the treatment of acute and chronic inflammatory diseases.

Item Type:

Journal Article (Review Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Topographical and Clinical Anatomy

UniBE Contributor:

Djonov, Valentin Georgiev and Volarevic, Vladislav

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0951-6433

Publisher:

Wiley

Language:

English

Submitter:

David Christian Haberthür

Date Deposited:

10 Dec 2020 17:13

Last Modified:

10 Dec 2020 17:22

Publisher DOI:

10.1002/biof.1587

PubMed ID:

31755595

Uncontrolled Keywords:

immunosuppression inflammation interleukin 1 receptor antagonist mesenchymal stem cells regeneration

BORIS DOI:

10.7892/boris.149210

URI:

https://boris.unibe.ch/id/eprint/149210

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