title: Neuropilin-1 Is Expressed on Lymphoid Tissue Residing LTi-like Group 3 Innate Lymphoid Cells and Associated with Ectopic Lymphoid Aggregates.
abstract: Here, we characterize a subset of ILC3s that express Neuropilin1 (NRP1) and are present in lymphoid tissues, but not in the peripheral blood or skin. NRP1+group 3 innate lymphoid cells (ILC3s) display in vitro lymphoid tissue inducer (LTi) activity. In agreement with this, NRP1+ILC3s are mainly located in proximity to high endothelial venules (HEVs) and express cell surface molecules involved in lymphocyte migration in secondary lymphoid tissues via HEVs. NRP1 was also expressed on mouse fetal LTi cells, indicating that NRP1 is a conserved marker for LTi cells. Human NRP1+ILC3s are primed cells because they express CD45RO and produce higher amounts of cytokines than NRP1-cells, which express CD45RA. The NRP1 ligand vascular endothelial growth factor A (VEGF-A) served as a chemotactic factor for NRP1+ILC3s. NRP1+ILC3s are present in lung tissues from smokers and patients with chronic obstructive pulmonary disease, suggesting a role in angiogenesis and/or the initiation of ectopic pulmonary lymphoid aggregates.
authors.affiliation: Department of Experimental Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands. Electronic address: m.m.shikhagaie@amc.uva.nl.
authors.forename: Medya Mara
authors.initials: MM
authors.lastname: Shikhagaie
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
authors.forename: Åsa K
authors.initials: ÅK
authors.lastname: Björklund
authors.affiliation: Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, 171 77 Stockholm, Sweden.
authors.forename: Jenny
authors.initials: J
authors.lastname: Mjösberg
authors.affiliation: Unit of Airway Inflammation, Department of Experimental Medical Sciences, Lund University, 221 84 Lund, Sweden.
authors.forename: Jonas S
authors.initials: JS
authors.lastname: Erjefält
authors.affiliation: Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1006 AN Amsterdam, the Netherlands.
authors.forename: Anne S
authors.initials: AS
authors.lastname: Cornelissen
authors.affiliation: Department of Experimental Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
authors.forename: Xavier Romero
authors.initials: XR
authors.lastname: Ros
authors.affiliation: Department of Experimental Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Bal
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1081 HV Amsterdam, the Netherlands.
authors.forename: Jasper J
authors.initials: JJ
authors.lastname: Koning
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1081 HV Amsterdam, the Netherlands.
authors.forename: Reina E
authors.initials: RE
authors.lastname: Mebius
authors.affiliation: Unit of Airway Inflammation, Department of Experimental Medical Sciences, Lund University, 221 84 Lund, Sweden.
authors.forename: Michiko
authors.initials: M
authors.lastname: Mori
authors.affiliation: Department of Experimental Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
authors.forename: Melanie
authors.initials: M
authors.lastname: Bruchard
authors.affiliation: Department of Experimental Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
authors.forename: Bianca
authors.initials: B
authors.lastname: Blom
authors.affiliation: Department of Experimental Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands. Electronic address: hergen.spits@amc.uva.nl.
authors.forename: Hergen
authors.initials: H
authors.lastname: Spits
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism*; D008221:Lymphoid Tissue / Q000378:metabolism*; D051379:Mice; D009389:Neovascularization, Pathologic / Q000378:metabolism; D039942:Neuropilin-1 / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D016207:Cytokines; D042461:Vascular Endothelial Growth Factor A; D039942:Neuropilin-1; D017493:Leukocyte Common Antigens
keywords: HEVs; ILC3; LA; LTi; NRP1; VEGF-A; chemotaxis; high endothelial venues; human innate lymphoid cells 3; lymphoid tissue inducer cells; neuropilin-1; smoke-induced pulmonary lymphoid aggregates; vascular endothelial growth factor A