Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

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

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Comparison of two different culture conditions for derivation of early hiPSC

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. M2-like macrophages are responsible for collagen degradation through a mannose receptor-mediated pathway

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Human embryonic stem cells in culture possess primary cilia with hedgehog signaling machinery

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Intracellular collagen degradation mediated by uPARAP/Endo180 is a major pathway of extracellular matrix turnover during malignancy

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. uPARAP/Endo180 is essential for cellular uptake of collagen and promotes fibroblast collagen adhesion

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Rare non-coding Desmoglein-2 variant contributes to Arrhythmogenic right ventricular cardiomyopathy

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Skin tape stripping: Which layers of the epidermis are removed?

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Collagen density regulates the activity of tumor-infiltrating T cells

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. The effect of anti-IL-17 treatment on the reaction to a nickel patch test in patients with allergic contact dermatitis

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

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.

Original languageEnglish
JournalJournal of Cell Biology
Volume218
Issue number1
Pages (from-to)333-349
ISSN0021-9525
DOIs
Publication statusPublished - 7 Jan 2019

ID: 55803717