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
Affiliations
Medya Mara Shikhagaie
Department of Experimental Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands
Åsa K. Björklund
Department of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden
Jenny Mjösberg
Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, 171 77 Stockholm, Sweden
Jonas S. Erjefält
Unit of Airway Inflammation, Department of Experimental Medical Sciences, Lund University, 221 84 Lund, Sweden
Anne S. Cornelissen
Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1006 AN Amsterdam, the Netherlands
Xavier Romero Ros
Department of Experimental Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands
Suzanne M. Bal
Department of Experimental Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands
Jasper J. Koning
Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1081 HV Amsterdam, the Netherlands
Reina E. Mebius
Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1081 HV Amsterdam, the Netherlands
Michiko Mori
Unit of Airway Inflammation, Department of Experimental Medical Sciences, Lund University, 221 84 Lund, Sweden
Melanie Bruchard
Department of Experimental Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands
Bianca Blom
Department of Experimental Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands
Hergen Spits
Department of Experimental Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands
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.
