Matrix bound nanovesicle-associated IL-33 activates a pro-remodeling macrophage phenotype via a non-canonical, ST2-independent pathway.

Autor: Hussey GS; McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 Technology Drive, Suite 300, Pittsburgh, PA 15219-3110, USA.; Department of Surgery, School of Medicine, University of Pittsburgh, University of Pittsburgh Medical Center Presbyterian Hospital, 200 Lothrop Street, Pittsburgh, PA 15213, USA., Dziki JL; McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 Technology Drive, Suite 300, Pittsburgh, PA 15219-3110, USA.; Department of Surgery, School of Medicine, University of Pittsburgh, University of Pittsburgh Medical Center Presbyterian Hospital, 200 Lothrop Street, Pittsburgh, PA 15213, USA., Lee YC; McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 Technology Drive, Suite 300, Pittsburgh, PA 15219-3110, USA.; Department of Bioengineering, University of Pittsburgh, 3700 O'Hara Street, Pittsburgh, PA, 15261, USA., Bartolacci JG; McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 Technology Drive, Suite 300, Pittsburgh, PA 15219-3110, USA.; Department of Bioengineering, University of Pittsburgh, 3700 O'Hara Street, Pittsburgh, PA, 15261, USA., Behun M; McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 Technology Drive, Suite 300, Pittsburgh, PA 15219-3110, USA., Turnquist HR; McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 Technology Drive, Suite 300, Pittsburgh, PA 15219-3110, USA.; Department of Surgery, School of Medicine, University of Pittsburgh, University of Pittsburgh Medical Center Presbyterian Hospital, 200 Lothrop Street, Pittsburgh, PA 15213, USA.; Thomas E. Starzl Transplantation Institute, University of Pittsburgh, University of Pittsburgh Medical Center Presbyterian Hospital, 200 Lothrop Street, Pittsburgh, PA 15213, USA.; Department of Immunology, School of Medicine, University of Pittsburgh, University of Pittsburgh Medical Center Presbyterian Hospital, 200 Lothrop Street, Pittsburgh, PA 15213, USA., Badylak SF; McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 Technology Drive, Suite 300, Pittsburgh, PA 15219-3110, USA.; Department of Surgery, School of Medicine, University of Pittsburgh, University of Pittsburgh Medical Center Presbyterian Hospital, 200 Lothrop Street, Pittsburgh, PA 15213, USA.; Department of Bioengineering, University of Pittsburgh, 3700 O'Hara Street, Pittsburgh, PA, 15261, USA.
Jazyk: angličtina
Zdroj: Journal of immunology and regenerative medicine [J Immunol Regen Med] 2019 Mar; Vol. 3, pp. 26-35. Date of Electronic Publication: 2019 Feb 01.
DOI: 10.1016/j.regen.2019.01.001
Abstrakt: The regenerative healing response of injured skeletal muscle is dependent upon an appropriately timed switch from a local type-I to a type-II immune response. Biologic scaffolds derived from extracellular matrix (ECM) have been shown to facilitate a macrophage phenotype transition that leads to downstream site-appropriate functional tissue deposition and myogenesis. However, the mechanisms by which ECM directs the switching of immune cell phenotype are only partially understood. Herein, we provide the first evidence that matrix bound nanovesicles (MBV) embedded within ECM-scaffolds are a rich and stable source of interleukin-33 (IL-33), an alarmin/cytokine with emerging reparative properties. We show that IL-33 encapsulated within MBV bypass the classical IL33/ST2 receptor signaling pathway to direct macrophage differentiation into the reparative, pro-remodeling M2 phenotype, which in turn facilitates myogenesis of skeletal muscle progenitor cells. Our results suggest the potential of IL-33 + MBV as a clinical therapy to augment the restorative efficacy of existing ECM-based and non-ECM based approaches.
Competing Interests: Competing Interests Statement: The authors declare that they have no competing interests.
Databáze: MEDLINE
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