TY - JOUR
T1 - Innate Immune Pathways Promote Oligodendrocyte Progenitor Cell Recruitment to the Injury Site in Adult Zebrafish Brain
AU - Sanchez-gonzalez, Rosario
AU - Koupourtidou, Christina
AU - Lepko, Tjasa
AU - Zambusi, Alessandro
AU - Novoselc, Klara Tereza
AU - Durovic, Tamara
AU - Aschenbroich, Sven
AU - Schwarz, Veronika
AU - Breunig, Christopher T.
AU - Straka, Hans
AU - Huttner, Hagen B.
AU - Irmler, Martin
AU - Beckers, Johannes
AU - Wurst, Wolfgang
AU - Zwergal, Andreas
AU - Schauer, Tamas
AU - Straub, Tobias
AU - Czopka, Tim
AU - Trümbach, Dietrich
AU - Götz, Magdalena
AU - Stricker, Stefan H.
AU - Ninkovic, Jovica
N1 - Funding Information:
We gratefully acknowledge funding to JN from the German Research foundation (DFG) by the SFB 870, SPP1757, TRR274; to MG the German Research foundation (DFG) by the SFB 870, and the ERC grant ChroNeuroRepair: GA No. 340793; Work in W. W. lab is by the German Science Foundation Collaborative Research Centre (CRC) 870; funds from the Bayerisches Staatsministerium für Bildung und Kultus, Wissenschaft und Kunst within Bavarian Research Network “Human Induced Pluripotent Stem Cells” (ForIPS) and (in part) by the Helmholtz Portfolio Theme ‘Supercomputing and Modelling for the Human Brain’ (SMHB). H.S. is supported by the DFG (CRC 870). Dr. Huttner was supported by a research grant from the German Research Foundation (DFG-HU1961/2-1).
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/2/2
Y1 - 2022/2/2
N2 - The oligodendrocyte progenitors (OPCs) are at the front of the glial reaction to the traumatic brain injury. However, regulatory pathways steering the OPC reaction as well as the role of reactive OPCs remain largely unknown. Here, we compared a long-lasting, exacerbated reaction of OPCs to the adult zebrafish brain injury with a timely restricted OPC activation to identify the specific molecular mechanisms regulating OPC reactivity and their contribution to regeneration. We demonstrated that the influx of the cerebrospinal fluid into the brain parenchyma after injury simultaneously activates the toll-like receptor 2 (Tlr2) and the chemokine receptor 3 (Cxcr3) innate immunity pathways, leading to increased OPC proliferation and thereby exacerbated glial reactivity. These pathways were critical for long-lasting OPC accumulation even after the ablation of microglia and infiltrating monocytes. Importantly, interference with the Tlr1/2 and Cxcr3 pathways after injury alleviated reactive gliosis, increased new neuron recruitment, and improved tissue restoration.
AB - The oligodendrocyte progenitors (OPCs) are at the front of the glial reaction to the traumatic brain injury. However, regulatory pathways steering the OPC reaction as well as the role of reactive OPCs remain largely unknown. Here, we compared a long-lasting, exacerbated reaction of OPCs to the adult zebrafish brain injury with a timely restricted OPC activation to identify the specific molecular mechanisms regulating OPC reactivity and their contribution to regeneration. We demonstrated that the influx of the cerebrospinal fluid into the brain parenchyma after injury simultaneously activates the toll-like receptor 2 (Tlr2) and the chemokine receptor 3 (Cxcr3) innate immunity pathways, leading to increased OPC proliferation and thereby exacerbated glial reactivity. These pathways were critical for long-lasting OPC accumulation even after the ablation of microglia and infiltrating monocytes. Importantly, interference with the Tlr1/2 and Cxcr3 pathways after injury alleviated reactive gliosis, increased new neuron recruitment, and improved tissue restoration.
U2 - 10.3390/cells11030520
DO - 10.3390/cells11030520
M3 - Article
VL - 11
JO - Cells
JF - Cells
SN - 2073-4409
IS - 3
M1 - 520
ER -