title: CXCL12a/CXCR4b acts to retain neutrophils in caudal hematopoietic tissue and to antagonize recruitment to an injury site in the zebrafish larva.
abstract: Neutrophils are a major component of the innate immune response and the most abundant circulating cell type in humans and zebrafish. The CXCL12/CXCR4 ligand receptor pair plays a key role in neutrophil homeostasis, controlling definitive hematopoiesis and neutrophil release into circulation. Neutrophils overexpressing CXCR4 respond by migrating towards sources of CXCL12, which is abundant in hematopoietic tissues. However, the physiological role of CXCL12/CXCR4 signaling during inflammatory responses remains unknown. Here, we show that zebrafish mutants lacking functional CXCL12a or CXCR4b show disrupted granulopoiesis in the kidney and increased number of circulating neutrophils. Additionally, CXCL12a and CXCR4b mutants display exacerbated recruitment of neutrophils to wounds and not to infections, and migrating neutrophils to wounds show increased directionality. Our results show that CXCL12a/CXCR4b signaling antagonizes wound-induced inflammatory signals by retaining neutrophils in hematopoietic tissues as a part of a balance between both inflammatory and anti-inflammatory cues, whose dynamic levels control neutrophils complex migratory behavior.
authors.affiliation: FONDAP Center for Genome Regulation, Facultad de Ciencias, Universidad de Chile, Casilla 653, Santiago, Chile.
authors.forename: Susana
authors.initials: S
authors.lastname: Paredes-Zúñiga
authors.affiliation: FONDAP Center for Genome Regulation, Facultad de Ciencias, Universidad de Chile, Casilla 653, Santiago, Chile.
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Morales
authors.affiliation: FONDAP Center for Genome Regulation, Facultad de Ciencias, Universidad de Chile, Casilla 653, Santiago, Chile.
authors.forename: Salomé
authors.initials: S
authors.lastname: Muñoz-Sánchez
authors.affiliation: FONDAP Center for Genome Regulation, Facultad de Ciencias, Universidad de Chile, Casilla 653, Santiago, Chile.
authors.forename: Carlos
authors.initials: C
authors.lastname: Muñoz-Montecinos
authors.affiliation: FONDAP Center for Genome Regulation, Facultad de Ciencias, Universidad de Chile, Casilla 653, Santiago, Chile.
authors.forename: Margarita
authors.initials: M
authors.lastname: Parada
authors.affiliation: FONDAP Center for Genome Regulation, Facultad de Ciencias, Universidad de Chile, Casilla 653, Santiago, Chile.
authors.forename: Karina
authors.initials: K
authors.lastname: Tapia
authors.affiliation: FONDAP Center for Genome Regulation, Facultad de Ciencias, Universidad de Chile, Casilla 653, Santiago, Chile.
authors.forename: Carlos
authors.initials: C
authors.lastname: Rubilar
authors.affiliation: FONDAP Center for Genome Regulation, Facultad de Ciencias, Universidad de Chile, Casilla 653, Santiago, Chile. mallende@uchile.cl.
authors.forename: Miguel L
authors.initials: ML
authors.lastname: Allende
authors.affiliation: FONDAP Center for Genome Regulation, Facultad de Ciencias, Universidad de Chile, Casilla 653, Santiago, Chile. uitlanders@gmail.com.|University College London, London, UK. uitlanders@gmail.com.
authors.forename: Oscar A
authors.initials: OA
authors.lastname: Peña
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000276:immunology*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis / Q000276:immunology*; D007249:Inflammation; D007814:Larva / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D019718:Receptors, CXCR4 / Q000276:immunology*; D015027:Zebrafish / Q000276:immunology* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000276:immunology*
chemical_list: C471276:CXCR4b protein, zebrafish; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; D029961:Zebrafish Proteins; C579453:cxcl12a protein, zebrafish
keywords: CXCL12; CXCR4; Inflammation; Neutrophil; Zebrafish