Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • 100th Anniversary of Insulin's Discovery (Jan 2021)
    • Hypoxia-inducible factors in disease pathophysiology and therapeutics (Oct 2020)
    • Latency in Infectious Disease (Jul 2020)
    • Immunotherapy in Hematological Cancers (Apr 2020)
    • Big Data's Future in Medicine (Feb 2020)
    • Mechanisms Underlying the Metabolic Syndrome (Oct 2019)
    • Reparative Immunology (Jul 2019)
    • View all review series ...
  • Viewpoint
  • Collections
    • Recently published
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • Recently published
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
Transcytosis route mediates rapid delivery of intact antibodies to draining lymph nodes
Laura Kähäri, … , Johanna Ivaska, Marko Salmi
Laura Kähäri, … , Johanna Ivaska, Marko Salmi
Published June 24, 2019
Citation Information: J Clin Invest. 2019;129(8):3086-3102. https://doi.org/10.1172/JCI125740.
View: Text | PDF
Research Article Immunology Vascular biology

Transcytosis route mediates rapid delivery of intact antibodies to draining lymph nodes

  • Text
  • PDF
Abstract

Lymph nodes (LNs) filter lymph to mount effective immune responses. Small soluble lymph-borne molecules from the periphery enter the draining LNs via a reticular conduit system. Intact antibodies and other larger molecules, in contrast, are physically unable to enter the conduits, and they are thought to be transported to the LNs only within migratory DCs after proteolytic degradation. Here, we discovered that lymph-borne antibodies and other large biomolecules enter within seconds into the parenchyma of the draining LN in an intact form. Mechanistically, we found that the uptake of large molecules is a receptor-independent, fluid-phase process that takes place by dynamin-dependent vesicular transcytosis through the lymphatic endothelial cells in the subcapsular sinus of the LN. Physiologically, this pathway mediates a very fast transfer of large protein antigens from the periphery to LN-resident DCs and macrophages. We show that exploitation of the transcytosis system allows enhanced whole-organ imaging and spatially controlled lymphocyte activation by s.c. administered antibodies in vivo. Transcytosis through the floor of the subcapsular sinus thus represents what we believe to be a new physiological and targetable mode of lymph filtering.

Authors

Laura Kähäri, Ruth Fair-Mäkelä, Kaisa Auvinen, Pia Rantakari, Sirpa Jalkanen, Johanna Ivaska, Marko Salmi

×

Figure 10

Fast delivery of large lymph-borne antigens to resident antigen-presenting cells in the draining LN.

Options: View larger image (or click on image) Download as PowerPoint
Fast delivery of large lymph-borne antigens to resident antigen-presenti...
(A–D) Uptake of Alexa Fluor 647–labeled AOC3 antigen (180 kDa) after s.c. administration (2-μg dose, t = 2 h) in resident DCs (resDCs) and macrophages in the draining LN. Uninjected LNs served as negative controls. (A) Gating strategy for identification of resident DCs, medullary sinus macrophages (MSMs), and nonsinusoidal resident macrophages (non-SMs). (B and C) Flow cytometric analyses (B) (n = 4), confocal analyses (C) (n = 2), and quantification of AOC3 uptake in resident DCs. Scale bars: 10 μm. (D) Flow cytometric analyses and quantification of AOC3 uptake in resident macrophage populations (n = 4). In the bar graphs, each dot represents 1 LN, and data are the mean ± SD. *P < 0.05, by Mann-Whitney U test.
Follow JCI:
Copyright © 2021 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts