Universität zu Köln

Knipper, Johanna A., Willenborg, Sebastian, Brinckmann, Juergen, Bloch, Wilhelm, Maass, Tobias, Wagener, Raimund, Krieg, Thomas, Sutherland, Tara ORCID: 0000-0001-9334-8206, Munitz, Ariel, Rothenberg, Marc E., Niehoff, Anja ORCID: 0000-0002-4165-0929, Richardson, Rebecca ORCID: 0000-0002-4701-8713, Hammerschmidt, Matthias, Allen, Judith E. and Eming, Sabine A. (2015). Interleukin-4 Receptor alpha Signaling in Myeloid Cells Controls Collagen Fibril Assembly in Skin Repair. Immunity, 43 (4). S. 803 - 817. CAMBRIDGE: CELL PRESS. ISSN 1097-4180

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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 alpha (IL-4R alpha)-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-alpha as one important player in the pathway from IL-4R alpha 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-beta 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Knipper, Johanna A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Willenborg, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Brinckmann, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Bloch, Wilhelm UNSPECIFIED UNSPECIFIED UNSPECIFIED Maass, Tobias UNSPECIFIED UNSPECIFIED UNSPECIFIED Wagener, Raimund UNSPECIFIED UNSPECIFIED UNSPECIFIED Krieg, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Sutherland, Tara UNSPECIFIED orcid.org/0000-0001-9334-8206 UNSPECIFIED Munitz, Ariel UNSPECIFIED UNSPECIFIED UNSPECIFIED Rothenberg, Marc E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Niehoff, Anja UNSPECIFIED orcid.org/0000-0002-4165-0929 UNSPECIFIED Richardson, Rebecca UNSPECIFIED orcid.org/0000-0002-4701-8713 UNSPECIFIED Hammerschmidt, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Allen, Judith E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Eming, Sabine A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-389560
DOI:	10.1016/j.immuni.2015.09.005
Journal or Publication Title:	Immunity
Volume:	43
Number:	4
Page Range:	S. 803 - 817
Date:	2015
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1097-4180
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TELOPEPTIDE LYSYL HYDROXYLASE; PYRIDINOLINE CROSS-LINKS; RESISTIN-LIKE MOLECULE; EXPRESSION; FIBROSIS; IMMUNITY; DISEASE; PATTERN; MATRIX Multiple languages Immunology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/38956