Forskning
Udskriv Udskriv
Switch language
Rigshospitalet - en del af Københavns Universitetshospital
Udgivet

Immune regulation by fibroblasts in tissue injury depends on uPARAP-mediated uptake of collectins

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Harvard

APA

CBE

MLA

Vancouver

Author

Bibtex

@article{dab78686def1477db1460ab293db9820,
title = "Immune regulation by fibroblasts in tissue injury depends on uPARAP-mediated uptake of collectins",
abstract = "Collectins such as mannose-binding lectin (MBL) and surfactant protein D (SP-D) become temporarily deposited in extravascular compartments after tissue injury and perform immune-stimulatory or inflammation-limiting functions. However, their turnover mechanisms, necessary to prevent excessive tissue damage, are virtually unknown. In this study, we show that fibroblasts in injured tissues undertake the clearance of collectins by using the endocytic collagen receptor uPARAP. In cellular assays, several types of collectins were endocytosed in a highly specific uPARAP-dependent process, not shared by the closely related receptor MR/CD206. When introduced into dermis or bleomycin-injured lungs of mice, collectins MBL and SP-D were endocytosed and routed for lysosomal degradation by uPARAP-positive fibroblasts. Fibroblast-specific expression of uPARAP governed endogenous SP-D levels and overall survival after lung injury. In lung tissue from idiopathic pulmonary fibrosis patients, a strong up-regulation of uPARAP was observed in fibroblasts adjacent to regions with SP-D secretion. This study demonstrates a novel immune-regulatory function of fibroblasts and identifies uPARAP as an endocytic receptor in immunity.",
keywords = "Animals, Bleomycin/administration & dosage, Bronchoalveolar Lavage Fluid/chemistry, Endocytosis, Fibroblasts/immunology, Gene Expression, Humans, Immunity, Innate, Interleukin-6/genetics, Lectins, C-Type/genetics, Lung Injury/chemically induced, Lung/immunology, Lysosomes/immunology, Mannose-Binding Lectin/genetics, Mannose-Binding Lectins/genetics, Membrane Glycoproteins/genetics, Mice, Mice, Inbred C57BL, Mice, Transgenic, Proteolysis, Pulmonary Fibrosis/chemically induced, Pulmonary Surfactant-Associated Protein D/genetics, Receptors, Cell Surface/genetics, Survival Analysis",
author = "J{\"u}rgensen, {Henrik J} and N{\o}rregaard, {Kirstine S} and Sibree, {Megan M} and Eric Santoni-Rugiu and Madsen, {Daniel H} and Katharina Wassilew and Dorrit Krustrup and Peter Garred and Bugge, {Thomas H} and Engelholm, {Lars H} and Niels Behrendt",
note = "{\circledC} 2018 J{\"u}rgensen et al.",
year = "2019",
month = "1",
day = "7",
doi = "10.1083/jcb.201802148",
language = "English",
volume = "218",
pages = "333--349",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "1",

}

RIS

TY - JOUR

T1 - Immune regulation by fibroblasts in tissue injury depends on uPARAP-mediated uptake of collectins

AU - Jürgensen, Henrik J

AU - Nørregaard, Kirstine S

AU - Sibree, Megan M

AU - Santoni-Rugiu, Eric

AU - Madsen, Daniel H

AU - Wassilew, Katharina

AU - Krustrup, Dorrit

AU - Garred, Peter

AU - Bugge, Thomas H

AU - Engelholm, Lars H

AU - Behrendt, Niels

N1 - © 2018 Jürgensen et al.

PY - 2019/1/7

Y1 - 2019/1/7

N2 - Collectins such as mannose-binding lectin (MBL) and surfactant protein D (SP-D) become temporarily deposited in extravascular compartments after tissue injury and perform immune-stimulatory or inflammation-limiting functions. However, their turnover mechanisms, necessary to prevent excessive tissue damage, are virtually unknown. In this study, we show that fibroblasts in injured tissues undertake the clearance of collectins by using the endocytic collagen receptor uPARAP. In cellular assays, several types of collectins were endocytosed in a highly specific uPARAP-dependent process, not shared by the closely related receptor MR/CD206. When introduced into dermis or bleomycin-injured lungs of mice, collectins MBL and SP-D were endocytosed and routed for lysosomal degradation by uPARAP-positive fibroblasts. Fibroblast-specific expression of uPARAP governed endogenous SP-D levels and overall survival after lung injury. In lung tissue from idiopathic pulmonary fibrosis patients, a strong up-regulation of uPARAP was observed in fibroblasts adjacent to regions with SP-D secretion. This study demonstrates a novel immune-regulatory function of fibroblasts and identifies uPARAP as an endocytic receptor in immunity.

AB - Collectins such as mannose-binding lectin (MBL) and surfactant protein D (SP-D) become temporarily deposited in extravascular compartments after tissue injury and perform immune-stimulatory or inflammation-limiting functions. However, their turnover mechanisms, necessary to prevent excessive tissue damage, are virtually unknown. In this study, we show that fibroblasts in injured tissues undertake the clearance of collectins by using the endocytic collagen receptor uPARAP. In cellular assays, several types of collectins were endocytosed in a highly specific uPARAP-dependent process, not shared by the closely related receptor MR/CD206. When introduced into dermis or bleomycin-injured lungs of mice, collectins MBL and SP-D were endocytosed and routed for lysosomal degradation by uPARAP-positive fibroblasts. Fibroblast-specific expression of uPARAP governed endogenous SP-D levels and overall survival after lung injury. In lung tissue from idiopathic pulmonary fibrosis patients, a strong up-regulation of uPARAP was observed in fibroblasts adjacent to regions with SP-D secretion. This study demonstrates a novel immune-regulatory function of fibroblasts and identifies uPARAP as an endocytic receptor in immunity.

KW - Animals

KW - Bleomycin/administration & dosage

KW - Bronchoalveolar Lavage Fluid/chemistry

KW - Endocytosis

KW - Fibroblasts/immunology

KW - Gene Expression

KW - Humans

KW - Immunity, Innate

KW - Interleukin-6/genetics

KW - Lectins, C-Type/genetics

KW - Lung Injury/chemically induced

KW - Lung/immunology

KW - Lysosomes/immunology

KW - Mannose-Binding Lectin/genetics

KW - Mannose-Binding Lectins/genetics

KW - Membrane Glycoproteins/genetics

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

KW - Proteolysis

KW - Pulmonary Fibrosis/chemically induced

KW - Pulmonary Surfactant-Associated Protein D/genetics

KW - Receptors, Cell Surface/genetics

KW - Survival Analysis

UR - http://www.scopus.com/inward/record.url?scp=85059926686&partnerID=8YFLogxK

U2 - 10.1083/jcb.201802148

DO - 10.1083/jcb.201802148

M3 - Journal article

VL - 218

SP - 333

EP - 349

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 1

ER -

ID: 55803717