Neuropilin-1 Is Expressed on Lymphoid Tissue Residing LTi-like Group 3 Innate Lymphoid Cells and Associated with Ectopic Lymphoid Aggregates

Medya Mara Shikhagaie; Åsa K Björklund; Jenny Mjösberg; Jonas S Erjefält; Anne S Cornelissen; Xavier Romero Ros; Suzanne M Bal; Jasper J Koning; Reina E Mebius; Michiko Mori; Melanie Bruchard; Bianca Blom; Hergen Spits

doi:10.1016/j.celrep.2017.01.063

Neuropilin-1 Is Expressed on Lymphoid Tissue Residing LTi-like Group 3 Innate Lymphoid Cells and Associated with Ectopic Lymphoid Aggregates

Cell Rep. 2017 Feb 14;18(7):1761-1773. doi: 10.1016/j.celrep.2017.01.063.

Authors

Affiliations

¹ Department of Experimental Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands. Electronic address: [email protected].
² Department of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
³ Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, 171 77 Stockholm, Sweden.
⁴ Unit of Airway Inflammation, Department of Experimental Medical Sciences, Lund University, 221 84 Lund, Sweden.
⁵ Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1006 AN Amsterdam, the Netherlands.
⁶ Department of Experimental Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
⁷ Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1081 HV Amsterdam, the Netherlands.
⁸ Department of Experimental Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands. Electronic address: [email protected].

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.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Movement / physiology
Cells, Cultured
Cytokines / metabolism
Humans
Leukocyte Common Antigens / metabolism
Lymphocytes / metabolism*
Lymphoid Tissue / metabolism*
Mice
Neovascularization, Pathologic / metabolism
Neuropilin-1 / metabolism*
Pulmonary Disease, Chronic Obstructive / metabolism
Vascular Endothelial Growth Factor A / metabolism

Substances

Cytokines
Vascular Endothelial Growth Factor A
Neuropilin-1
Leukocyte Common Antigens