| First Author | Knipper JA | Year | 2015 |
| Journal | Immunity | Volume | 43 |
| Issue | 4 | Pages | 803-16 |
| PubMed ID | 26474656 | Mgi Jnum | J:233919 |
| Mgi Id | MGI:5788376 | Doi | 10.1016/j.immuni.2015.09.005 |
| Citation | Knipper JA, et al. (2015) Interleukin-4 Receptor alpha Signaling in Myeloid Cells Controls Collagen Fibril Assembly in Skin Repair. Immunity 43(4):803-16 |
| abstractText | 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-4Ralpha)-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-4Ralpha 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. |
