Significance: Keratinocytes, a major cellular component of the epidermis, are responsible for restoring the epidermis after injury through a process termed epithelialization. This review will focus on the pivotal role of keratinocytes in epithelialization, including cellular processes and mechanisms of their regulation during re-epithelialization, and their cross talk with other cell types participating in wound healing. Recent Advances: Discoveries in epidermal stem cells, keratinocyte immune function, and the role of the epidermis as an independent neuroendocrine organ will be reviewed. Novel mechanisms of gene expression regulation important for re-epithelialization, including microRNAs and histone modifications, will also be discussed. Critical Issues: Epithelialization is an essential component of wound healing used as a defining parameter of a successful wound closure. A wound cannot be considered healed in the absence of re-epithelialization. The epithelialization process is impaired in all types o...

Epithelialization in Wound Healing: A Comprehensive Review

Combination Cancer Therapy with Immune Checkpoint Blockade: Mechanisms and Strategies.

The innate immune system, toll-like receptors and dermal wound healing: A review.

Significance: Inflammation is an integral part of immune response and supports optimal wound healing in adults Inflammatory cells such as neutrophils, macrophages, dendritic cells, lymphocytes, and mast cells produce important cytokines, chemokines, and growth factors These immune cells interact with keratinocytes, fibroblasts, and endothelial cells (ECs), as well as the extracellular matrix within a complicated network that promotes and regulates wound healing Aberrant and persistent inflammation may result in delayed wound healing, scar formation, or chronic wounds Targeting the molecules involved in the inflammatory response may have great potential therapeutic value Recent Advances and Critical Issues: Toll-like receptors (TLRs) are pattern recognition receptors that recognize pathogen-associated molecular patterns from microbes or danger-associated molecular patterns from damaged cells The discovery of TLRs sheds new light on the mechanism by which the inflammatory or innate immune response is initiated in wound healing Convincing evidence now shows that multiple types of cells, including infiltrating or resident inflammatory cells, keratinocytes, fibroblasts, and ECs, express specific types of TLRs Experimental reduction of certain TLRs or treatment of wounds with TLR ligands has been shown to affect wound healing A better understanding of the involvement of TLRs in the innate immune response during skin wound healing may suggest novel strategies to improve the quality of tissue repair Future Directions: Despite the indisputable role of TLRs in regulating the immune response in acute wound healing, the functions of TLRs that are relevant to human wound healing and chronic wounds are poorly understood

/pdf/toll-like-receptor-function-in-acute-wounds-57iupd33wy.pdf

Toll-Like Receptor Function in Acute Wounds.

Toll-like receptors (TLRs) are innate receptors critical for host defense, and play a role in normal biological processes. For example, host DNA, a TLR9 ligand, stimulates epithelial repair following skin wounding. TLR signaling also plays a crucial role in regulating intestinal homeostasis. We therefore asked whether TLR9 is important for intestinal wound repair using a dextran sulfate sodium (DSS)-induced intestinal damage and repair model. We showed that TLR9-deficient mice are more susceptible to DSS, and exhibited delayed wound repair at both the clinical and histologic levels. TLR9-deficient mice showed reduced gene expression of hairy enhancer of split 1, an intestinal progenitor cell differentiation factor, and vascular endothelial growth factor, a growth factor important for epithelial cell restitution. Therefore, we conclude that TLR stimulation may play a normal role in regulating intestinal homeostasis and could potentially be a novel therapeutic target to enhance intestinal wound repair in inflammatory bowel diseases.

/pdf/tlr9-is-important-for-protection-against-intestinal-damage-3oht5rrdd3.pdf

TLR9 is important for protection against intestinal damage and for intestinal repair

Accelerated wound healing mediated by activation of Toll-like receptor 9

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Accelerated wound healing mediated by activation of Toll-like receptor 9