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

Johanna A Knipper, Sebastian Willenborg, Jürgen Brinckmann, Wilhelm Bloch, Tobias Maaß, Raimund Wagener, Thomas Krieg, Tara Sutherland, Ariel Munitz, Marc E Rothenberg, Anja Niehoff, Rebecca Richardson, Matthias Hammerschmidt, Judith E Allen, Sabine A Eming

Research output: Contribution to journalArticlepeer-review

208 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)803-816
Number of pages14
Issue number4
Early online date17 Oct 2015
Publication statusPublished - 20 Oct 2015


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