Single-Cell Survey of Human Lymphatics Unveils Marked Endothelial Cell Heterogeneity and Mechanisms of Homing for Neutrophils.

Abstract:

: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.

journal_name

Immunity

journal_title

Immunity

authors

Takeda A,Hollmén M,Dermadi D,Pan J,Brulois KF,Kaukonen R,Lönnberg T,Boström P,Koskivuo I,Irjala H,Miyasaka M,Salmi M,Butcher EC,Jalkanen S

doi

10.1016/j.immuni.2019.06.027

subject

Has Abstract

pub_date

2019-09-17 00:00:00

pages

561-572.e5

issue

3

eissn

1074-7613

issn

1097-4180

pii

S1074-7613(19)30297-3

journal_volume

51

pub_type

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