The Role of an IL-10/Hyaluronan Axis in Dermal Wound Healing.

Kavya L Singampalli,Paul L Bollyky,Sundeep G Keswani,Ravi K Birla,Xinyi Wang,Swathi Balaji,Aditya Kaul,Umang M Parikh,Jamie Gilley

doi:10.3389/fcell.2020.00636

Abstract

Scar formation is the typical endpoint of postnatal dermal wound healing, which affects more than 100 million individuals annually. Not only do scars cause a functional burden by reducing the biomechanical strength of skin at the site of injury, but they also significantly increase healthcare costs and impose psychosocial challenges. Though the mechanisms that dictate how dermal wounds heal are still not completely understood, they are regulated by extracellular matrix (ECM) remodeling, neovascularization, and inflammatory responses. The cytokine interleukin (IL)-10 has emerged as a key mediator of the pro- to anti-inflammatory transition that counters collagen deposition in scarring. In parallel, the high molecular weight (HMW) glycosaminoglycan hyaluronan (HA) is present in the ECM and acts in concert with IL-10 to block pro-inflammatory signals and attenuate fibrotic responses. Notably, high concentrations of both IL-10 and HMW HA are produced in early gestational fetal skin, which heals scarlessly. Since fibroblasts are responsible for collagen deposition, it is critical to determine how the concerted actions of IL-10 and HA drive their function to potentially control fibrogenesis. Beyond their independent actions, an auto-regulatory IL-10/HA axis may exist to modulate the magnitude of CD4+ effector T lymphocyte activation and enhance T regulatory cell function in order to reduce scarring. This review underscores the pathophysiological impact of the IL-10/HA axis as a multifaceted molecular mechanism to direct primary cell responders and regulators toward either regenerative dermal tissue repair or scarring.

Highlights

Scar formation is the typical endpoint of postnatal dermal wound healing, which affects more than 100 million individuals annually
In contrast to postnatal skin, fetal tissues and adult mucosal tissues feature lower inflammatory responses underscored by reduced immune cell recruitment and activation, lower transforming growth factor (TGF) -β1 levels (Whitby and Ferguson, 1991), and increased vascular maturity and keratinocyte proliferation (Glim et al, 2014; DiPietro, 2016); all of which are consistent with regenerative wound healing
The present review aims to address the morbidity of fibrosis as it relates to differences between tissue types and the contribution of immune cell responders to extracellular matrix (ECM) remodeling, with specific notes on the role of IL-10 and HA in modulating fibroblast response to injury and the potential physiological impact of T lymphocyte driven regulation

Summary

Introduction

Scar formation is the typical endpoint of postnatal dermal wound healing, which affects more than 100 million individuals annually. In contrast to postnatal skin, fetal tissues and adult mucosal tissues feature lower inflammatory responses underscored by reduced immune cell recruitment and activation, lower transforming growth factor (TGF) -β1 levels (Whitby and Ferguson, 1991), and increased vascular maturity and keratinocyte proliferation (Glim et al, 2014; DiPietro, 2016); all of which are consistent with regenerative wound healing.

Results

Conclusion