GARP Regulates the Immune Capacity of a Human Autologous Platelet Concentrate

Autologous platelet concentrates, like liquid platelet rich fibrin (iPRF), optimize wound healing; however, the underlying immunological mechanisms are poorly understood. Platelets, the main cellular component of iPRF, highly express the protein, Glycoprotein A repetitions predominant (GARP), on the...

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Main Authors: Emily R. Trzeciak, Niklas Zimmer, Peer W. Kämmerer, Daniel Thiem, Bilal Al-Nawas, Andrea Tuettenberg, Sebastian Blatt
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/10/12/3136
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author Emily R. Trzeciak
Niklas Zimmer
Peer W. Kämmerer
Daniel Thiem
Bilal Al-Nawas
Andrea Tuettenberg
Sebastian Blatt
author_facet Emily R. Trzeciak
Niklas Zimmer
Peer W. Kämmerer
Daniel Thiem
Bilal Al-Nawas
Andrea Tuettenberg
Sebastian Blatt
author_sort Emily R. Trzeciak
collection DOAJ
description Autologous platelet concentrates, like liquid platelet rich fibrin (iPRF), optimize wound healing; however, the underlying immunological mechanisms are poorly understood. Platelets, the main cellular component of iPRF, highly express the protein, Glycoprotein A repetitions predominant (GARP), on their surfaces. GARP plays a crucial role in maintaining peripheral tolerance, but its influence on the immune capacity of iPRF remains unclear. This study analyzed the interaction of iPRF with immune cells implicated in the wound healing process (human monocyte derived macrophages and CD4<sup>+</sup> T cells) and evaluated the distinct influence of GARP on these mechanisms in vitro. GARP was determined to be expressed on the surface of platelets and to exist as a soluble factor in iPRF. Platelets derived from iPRF and iPRF itself induced a regulatory phenotype in CD4<sup>+</sup> T cells, shown by increased expression of Foxp3 and GARP as well as decreased production of IL-2 and IFN-γ. Application of an anti-GARP antibody reversed these effects. Additionally, iPRF polarized macrophages to a “M0/M2-like” phenotype in a GARP independent manner. Altogether, this study demonstrated for the first time that the immune capacity of iPRF is mediated in part by GARP and its ability to induce regulatory CD4<sup>+</sup> T cells.
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spelling doaj.art-3e522124c1e04649b30f383d503e46e82023-11-24T13:27:28ZengMDPI AGBiomedicines2227-90592022-12-011012313610.3390/biomedicines10123136GARP Regulates the Immune Capacity of a Human Autologous Platelet ConcentrateEmily R. Trzeciak0Niklas Zimmer1Peer W. Kämmerer2Daniel Thiem3Bilal Al-Nawas4Andrea Tuettenberg5Sebastian Blatt6Department of Dermatology, University Medical Center Mainz, Johannes Gutenberg University Mainz, 55131 Mainz, Rhineland-Palatinate, GermanyDepartment of Dermatology, University Medical Center Mainz, Johannes Gutenberg University Mainz, 55131 Mainz, Rhineland-Palatinate, GermanyDepartment of Oral and Maxillofacial Surgery, University Medical Center Mainz, Johannes Gutenberg University Mainz, 55131 Mainz, Rhineland-Palatinate, GermanyDepartment of Oral and Maxillofacial Surgery, University Medical Center Mainz, Johannes Gutenberg University Mainz, 55131 Mainz, Rhineland-Palatinate, GermanyDepartment of Oral and Maxillofacial Surgery, University Medical Center Mainz, Johannes Gutenberg University Mainz, 55131 Mainz, Rhineland-Palatinate, GermanyDepartment of Dermatology, University Medical Center Mainz, Johannes Gutenberg University Mainz, 55131 Mainz, Rhineland-Palatinate, GermanyDepartment of Oral and Maxillofacial Surgery, University Medical Center Mainz, Johannes Gutenberg University Mainz, 55131 Mainz, Rhineland-Palatinate, GermanyAutologous platelet concentrates, like liquid platelet rich fibrin (iPRF), optimize wound healing; however, the underlying immunological mechanisms are poorly understood. Platelets, the main cellular component of iPRF, highly express the protein, Glycoprotein A repetitions predominant (GARP), on their surfaces. GARP plays a crucial role in maintaining peripheral tolerance, but its influence on the immune capacity of iPRF remains unclear. This study analyzed the interaction of iPRF with immune cells implicated in the wound healing process (human monocyte derived macrophages and CD4<sup>+</sup> T cells) and evaluated the distinct influence of GARP on these mechanisms in vitro. GARP was determined to be expressed on the surface of platelets and to exist as a soluble factor in iPRF. Platelets derived from iPRF and iPRF itself induced a regulatory phenotype in CD4<sup>+</sup> T cells, shown by increased expression of Foxp3 and GARP as well as decreased production of IL-2 and IFN-γ. Application of an anti-GARP antibody reversed these effects. Additionally, iPRF polarized macrophages to a “M0/M2-like” phenotype in a GARP independent manner. Altogether, this study demonstrated for the first time that the immune capacity of iPRF is mediated in part by GARP and its ability to induce regulatory CD4<sup>+</sup> T cells.https://www.mdpi.com/2227-9059/10/12/3136iPRFliquid platelet rich fibrinautologous platelet concentratewound healingGARPTGF-ß
spellingShingle Emily R. Trzeciak
Niklas Zimmer
Peer W. Kämmerer
Daniel Thiem
Bilal Al-Nawas
Andrea Tuettenberg
Sebastian Blatt
GARP Regulates the Immune Capacity of a Human Autologous Platelet Concentrate
Biomedicines
iPRF
liquid platelet rich fibrin
autologous platelet concentrate
wound healing
GARP
TGF-ß
title GARP Regulates the Immune Capacity of a Human Autologous Platelet Concentrate
title_full GARP Regulates the Immune Capacity of a Human Autologous Platelet Concentrate
title_fullStr GARP Regulates the Immune Capacity of a Human Autologous Platelet Concentrate
title_full_unstemmed GARP Regulates the Immune Capacity of a Human Autologous Platelet Concentrate
title_short GARP Regulates the Immune Capacity of a Human Autologous Platelet Concentrate
title_sort garp regulates the immune capacity of a human autologous platelet concentrate
topic iPRF
liquid platelet rich fibrin
autologous platelet concentrate
wound healing
GARP
TGF-ß
url https://www.mdpi.com/2227-9059/10/12/3136
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