Bibliographic Details
| Title: |
IFN-κ is critical for normal wound repair and is decreased in diabetic wounds |
| Authors: |
Sonya J. Wolf, Christopher O. Audu, Amrita Joshi, Aaron denDekker, William J. Melvin, Frank M. Davis, Xianying Xing, Rachael Wasikowski, Lam C. Tsoi, Steven L. Kunkel, Johann E. Gudjonsson, Mary X. O’Riordan, J. Michelle Kahlenberg, Katherine A. Gallagher |
| Source: |
JCI Insight, Vol 7, Iss 9 (2022) |
| Publisher Information: |
American Society for Clinical investigation, 2022. |
| Publication Year: |
2022 |
| Collection: |
LCC:Medicine |
| Subject Terms: |
Inflammation, Medicine |
| More Details: |
Wound repair following acute injury requires a coordinated inflammatory response. Type I IFN signaling is important for regulating the inflammatory response after skin injury. IFN-κ, a type I IFN, has recently been found to drive skin inflammation in lupus and psoriasis; however, the role of IFN-κ in the context of normal or dysregulated wound healing is unclear. Here, we show that Ifnk expression is upregulated in keratinocytes early after injury and is essential for normal tissue repair. Under diabetic conditions, IFN-κ was decreased in wound keratinocytes, and early inflammation was impaired. Furthermore, we found that the histone methyltransferase mixed-lineage leukemia 1 (MLL1) is upregulated early following injury and regulates Ifnk expression in diabetic wound keratinocytes via an H3K4me3-mediated mechanism. Using a series of in vivo studies with a geneticall y engineered mouse model (Mll1fl/fl K14cre–) and human wound tissues from patients with T2D, we demonstrate that MLL1 controls wound keratinocyte–mediated Ifnk expression and that Mll1 expression is decreased in T2D keratinocytes. Importantly, we found the administration of IFN-κ early following injury improves diabetic tissue repair through increasing early inflammation, collagen deposition, and reepithelialization. These findings have significant implications for understanding the complex role type I IFNs play in keratinocytes in normal and diabetic wound healing. Additionally, they suggest that IFN may be a viable therapeutic target to improve diabetic wound repair. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2379-3708 |
| Relation: |
https://doaj.org/toc/2379-3708 |
| DOI: |
10.1172/jci.insight.152765 |
| Access URL: |
https://doaj.org/article/eca6cf178c67407eb93d2292893b3a0c |
| Accession Number: |
edsdoj.6cf178c67407eb93d2292893b3a0c |
| Database: |
Directory of Open Access Journals |
