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

Knipper JA, Willenborg S, Brinckmann J, Bloch W, Maaß T, Wagener R, Krieg T, Sutherland T, Munitz A, Rothenberg ME, Niehoff A, Richardson R, Hammerschmidt M, Allen JE, Eming SA

Immunity 2015 Oct;43(4):803-16

PMID: 26474656

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.

  • Upcoming Events

    1. Klenk Symposium 2017 – Tissue regeneration, wound healing and fibrosis: Translating basic concepts into regenerative therapy

      Oktober 15 - Oktober 17
  • News

© 2017 SFB 829