Format

Send to

Choose Destination
Immunity. 2015 Oct 20;43(4):803-16. doi: 10.1016/j.immuni.2015.09.005.

Interleukin-4 Receptor α Signaling in Myeloid Cells Controls Collagen Fibril Assembly in Skin Repair.

Author information

1
Department of Dermatology, University of Cologne, 50937 Cologne, Germany.
2
Department of Dermatology and Institute of Virology and Cell Biology, University of Lübeck, 23562 Lübeck, Germany.
3
Department of Molecular and Cellular Sport Medicine, German Sport University Cologne, 50933 Cologne, Germany.
4
Department of Biochemistry, University of Cologne, 50937 Cologne, Germany.
5
Department of Dermatology, University of Cologne, 50937 Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50674 Cologne, Germany.
6
Institute of Immunology and Infection Research, Centre for Immunity, Infection & Evolution, School of Biological Sciences, University of Edinburgh, EH9 3FL Edinburgh, UK.
7
Department of Clinical Microbiology and Immunology, The Sackler School of Medicine, The Tel-Aviv University, Ramat Aviv 69978, Israel.
8
Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229-3039, USA.
9
Institute of Biomechanics & Orthopedics, German Sport University Cologne, 50933 Cologne, Germany; Cologne Center for Musculoskeletal Biomechanics, University of Cologne, 50931 Cologne, Germany.
10
Institute of Developmental Biology, University of Cologne, 50674 Cologne, Germany.
11
Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50674 Cologne, Germany; Institute of Developmental Biology, University of Cologne, 50674 Cologne, Germany.
12
Department of Dermatology, University of Cologne, 50937 Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50674 Cologne, Germany. Electronic address: sabine.eming@uni-koeln.de.

Abstract

Activation of the immune response during injury is a critical early event that determines whether the outcome of tissue restoration is regeneration or replacement of the damaged tissue with a scar. The mechanisms by which immune signals control these fundamentally different regenerative pathways are largely unknown. We have demonstrated that, during skin repair in mice, interleukin-4 receptor α (IL-4Rα)-dependent macrophage activation controlled collagen fibril assembly and that this process was important for effective repair while having adverse pro-fibrotic effects. We identified Relm-α as one important player in the pathway from IL-4Rα signaling in macrophages to the induction of lysyl hydroxylase 2 (LH2), an enzyme that directs persistent pro-fibrotic collagen cross-links, in fibroblasts. Notably, Relm-β induced LH2 in human fibroblasts, and expression of both factors was increased in lipodermatosclerosis, a condition of excessive human skin fibrosis. Collectively, our findings provide mechanistic insights into the link between type 2 immunity and initiation of pro-fibrotic pathways.

PMID:
26474656
PMCID:
PMC4681399
DOI:
10.1016/j.immuni.2015.09.005
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center