A novel monocyte-derived antigen presenting cell-T regulatory cell axis contributes to skin wound healing and is impaired in diabetic mice
Year: 2026
Type: article
Abstract: Despite a vast literature on the role of macrophages in wound healing, the role of dermal monocyte (Mo)-derived antigen presenting cells (APC) has received scant attention. Using scRNAseq and flow cytometry, we identify a population of APC that is prominent in wounds of non-diabetic mice but is reduced in wounds of diabetic mice. Using adoptive transfer experiments and Ccr2 knockout mice, we demonstrate that wound APC are derived primarily from Mo and that the diabetic wound environment inhibits differentiation of Mo into APC. We also show that Mo-specific Irf4 knockout mice exhibit reduced differentiation of Mo into APC, decreased levels of IL-27 and numbers of activated Treg cells in wounds. and impaired wound healing. Importantly, adoptive transfer of bone marrow Mo that express Irf4 into wounds of Mo-specific Irf4 knockout mice rescued levels of wound APC and activated Treg, as well as wound healing. Local administration of recombinant IL-27 into wounds of these mice also rescued levels of activated Treg in wounds, along with wound healing, Together, these findings identify a novel pathway in which IRF4 induces Mo differentiation into APC in wounds, which in turn produce IL27 that activates Treg to promote healing. This pathway is impaired in wounds of diabetic mice, which provides a novel target to improve diabetic wound healing.
Source: The Journal of Immunology
Authors: Jingbo Pang, Brandon Lukas, Rita Roberts, Mark Maienschein-Cline, Yang Dai, Timothy J Koh
Institution: University of Illinois Chicago
Language: English
Topic: Wound Healing and Treatments
Subfield: Rehabilitation
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,500
Awards: G3465501189, G797306165
OpenAlex ID: W7164748922
