A1 Refereed original research article in a scientific journal
Gene-expression profiling of different arms of lymphatic vasculature identifies candidates for manipulation of cell traffic
Authors: Iftakhar-E-Khuda I, Fair-Makela R, Kukkonen-Macchi A, Elima K, Karikoski M, Rantakari P, Miyasaka M, Salmi M, Jalkanen S
Publisher: NATL ACAD SCIENCES
Publication year: 2016
Journal: Proceedings of the National Academy of Sciences of the United States of America
Journal name in source: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Journal acronym: P NATL ACAD SCI USA
Volume: 113
Issue: 38
First page : 10643
Last page: 10648
Number of pages: 6
ISSN: 0027-8424
DOI: https://doi.org/10.1073/pnas.1602357113
Web address : http://www.pnas.org/content/113/38/10643
Afferent lymphatic vessels bring antigens and diverse populations of leukocytes to draining lymph nodes, whereas efferent lymphatics allow only lymphocytes and antigens to leave the nodes. Despite the fundamental importance of afferent vs. efferent lymphatics in immune response and cancer spread, the molecular characteristics of these different arms of the lymphatic vasculature are largely unknown. The objective of this work was to explore molecular differences behind the distinct functions of afferent and efferent lymphatic vessels, and find possible molecules mediating lymphocyte traffic. We used laser-capture microdissection and cell sorting to isolate lymphatic endothelial cells (LECs) from the subcapsular sinus (SS, afferent) and lymphatic sinus (LS, efferent) for transcriptional analyses. The results reveal marked differences between afferent and efferent LECs and identify molecules on lymphatic vessels. Further characterizations of Siglec-1 (CD169) and macrophage scavenger receptor 1 (MSR1/CD204), show that they are discriminatively expressed on lymphatic endothelium of the SS but not on lymphatic vasculature of the LS. In contrast, endomucin (EMCN) is present on the LS endothelium and not on lymphatic endothelium of the SS. Moreover, both murine and human MSR1 on lymphatic endothelium of the SS bind lymphocytes and in in vivo studies MSR1 regulates entrance of lymphocytes from the SS to the lymph node parenchyma. In conclusion, this paper reports surprisingly distinct molecular profiles for afferent and efferent lymphatics and a function for MSR1. These results may open avenues to explore some of the now-identified molecules as targets to manipulate the function of lymphatic vessels.
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