Single-Cell Survey of Human Lymphatics Unveils Marked Endothelial Cell Heterogeneity and Mechanisms of Homing for Neutrophils.
Akira Takeda, Maija Hollmén, Denis Dermadi, Junliang Pan, Kevin Francis Brulois, Riina Kaukonen, Tapio Lönnberg, Pia Boström, Ilkka Koskivuo, Heikki Irjala, Masayuki Miyasaka, Marko Salmi, Eugene C Butcher, Sirpa Jalkanen
Author Information
- Akira Takeda: MediCity Research Laboratory and Institute of Biomedicine, University of Turku, Turku, Finland.
- Maija Hollmén: MediCity Research Laboratory and Institute of Biomedicine, University of Turku, Turku, Finland.
- Denis Dermadi: Laboratory of Immunology and Vascular Biology, Department of Pathology, School of Medicine, Stanford University, Stanford, CA, USA.
- Junliang Pan: Laboratory of Immunology and Vascular Biology, Department of Pathology, School of Medicine, Stanford University, Stanford, CA, USA; Veterans Affairs Palo Alto Health Care System and The Palo Alto Veterans Institute for Research, Palo Alto, CA, USA.
- Kevin Francis Brulois: Laboratory of Immunology and Vascular Biology, Department of Pathology, School of Medicine, Stanford University, Stanford, CA, USA.
- Riina Kaukonen: Turku Centre for Biotechnology, University of Turku, Turku, Finland.
- Tapio Lönnberg: Turku Centre for Biotechnology, University of Turku, Turku, Finland.
- Pia Boström: Department of Pathology, Turku University Hospital, Turku, Finland.
- Ilkka Koskivuo: Department of Plastic and General Surgery, Turku University Hospital, Turku, Finland.
- Heikki Irjala: Department of Otorhinolaryngology, Turku University Hospital and University of Turku, Finland.
- Masayuki Miyasaka: MediCity Research Laboratory and Institute of Biomedicine, University of Turku, Turku, Finland; Interdisciplinary Program for Biomedical Sciences, Institute for Academic Initiatives, Osaka University, Suita, Japan.
- Marko Salmi: MediCity Research Laboratory and Institute of Biomedicine, University of Turku, Turku, Finland.
- Eugene C Butcher: Laboratory of Immunology and Vascular Biology, Department of Pathology, School of Medicine, Stanford University, Stanford, CA, USA; Veterans Affairs Palo Alto Health Care System and The Palo Alto Veterans Institute for Research, Palo Alto, CA, USA.
- Sirpa Jalkanen: MediCity Research Laboratory and Institute of Biomedicine, University of Turku, Turku, Finland. Electronic address: sirjal@utu.fi.
Lymphatic vessels form a critical component in the regulation of human health and disease. While their functional significance is increasingly being recognized, the comprehensive heterogeneity of lymphatics remains uncharacterized. Here, we report the profiling of 33,000 lymphatic endothelial cells (LECs) in human lymph nodes (LNs) by single-cell RNA sequencing. Unbiased clustering revealed six major types of human LECs. LECs lining the subcapsular sinus (SCS) of LNs abundantly expressed neutrophil chemoattractants, whereas LECs lining the medullary sinus (MS) expressed a C-type lectin CD209. Binding of a carbohydrate Lewis X (CD15) to CD209 mediated neutrophil binding to the MS. The neutrophil-selective homing by MS LECs may retain neutrophils in the LN medulla and allow lymph-borne pathogens to clear, preventing their spread through LNs in humans. Our study provides a comprehensive characterization of LEC heterogeneity and unveils a previously undefined role for medullary LECs in human immunity.
Animals
Cell Adhesion Molecules
Cells, Cultured
Endothelial Cells
Humans
Lectins, C-Type
Lewis X Antigen
Lymph Nodes
Lymphatic Vessels
Mice, Inbred C57BL
Neutrophils
Receptors, Cell Surface
Surveys and Questionnaires
Cell Adhesion Molecules
DC-specific ICAM-3 grabbing nonintegrin
Lectins, C-Type
Lewis X Antigen
Receptors, Cell Surface
