PD-L1 Triggered by Binding eIF3I Contributes to the Amelioration of Diabetes-Associated Wound Healing Defects by Regulating IRS4

Cellular therapeutics and immunotherapies in wound healing – on the pulse of time?

“…Moreover, histological and quantitative polymerase chain reaction analysis revealed markedly reduced levels of inflammatory markers such as TNF-a, IL-6, and granzyme B, as well as diminished immune infiltration, in PD-L1 treatment groups relative to control [ 118 ]. Following these findings, Kuai et al [ 27 ] studied external PD-L1 application in a murine model of diabetic ulcers. The authors reported that diabetic ulcers underwent PD-L1 downregulation relative to normal wounds and proposed that endogenous PD-L1 deficiency may be a potential contributor to impaired healing in this context.…”

“…However, the authors noted that further research into the most effective dose is warranted [ 25 ] Polyclonal antibodies N/A Polyclonal antibodies are used, for example, to target the N-terminal of Pseudomonas aeruginosa ( P. aeruginosa ) type b flagellin in infected burn wounds and also to inactivate pathogenic toxins Pre-clinical murine model N/A The study was only pre-clinical and had a small sample size. It should be noted that there was no difference in mortality and wound healing time between anti- P. aeruginosa antibody treatment and imipenem antibiotic treatment [ 26 ] Monoclonal antibodies N/A Topical programmed death-ligand 1 (PD-L1) is a checkpoint inhibitor that can, applied as a gel, support re-epithelialization and attenuating prolonged inflammation Pre-clinical murine model N/A The study was only pre-clinical and had a small sample size [ 27 ] Wnt inhibitor Pyrvinium Pyrvinium, at least in pre-clinical studies, may enhance MSC proliferation, engraftment, and stemness in an in-vitro and in-vivo wound healing model. Pyrvinium was separately found to increase vascularity, cellular proliferation, and general organization of granulation tissue in a polyvinyl alcohol (PVA) sponge model.…”

Macrophages in Skin Wounds: Functions and Therapeutic Potential

“…Overall, the above study indicates that PD-1L helps to regulate Treg and Teff cells’ recruitment and targeting PD-1/PD-1L can influence the immune landscape in various diseases, such as chronic wound healing. To this end, it was shown that diabetic non-healing wounds had downregulated PD-1L [ 141 ]. Topical applications of exogeneous PD-1L enhanced the closure of diabetic wounds in parallel with the resolution of hyperinflammation and reduced macrophage cell numbers [ 141 ].…”

“…To this end, it was shown that diabetic non-healing wounds had downregulated PD-1L [ 141 ]. Topical applications of exogeneous PD-1L enhanced the closure of diabetic wounds in parallel with the resolution of hyperinflammation and reduced macrophage cell numbers [ 141 ]. Interestingly, the activation of PD-1L also promoted keratinocyte proliferation and migration, highlighting the diverse role of PD-1/PD-1L in non-immune cells [ 141 ].…”

“…Topical applications of exogeneous PD-1L enhanced the closure of diabetic wounds in parallel with the resolution of hyperinflammation and reduced macrophage cell numbers [ 141 ]. Interestingly, the activation of PD-1L also promoted keratinocyte proliferation and migration, highlighting the diverse role of PD-1/PD-1L in non-immune cells [ 141 ]. PD-1 is known to be expressed in myeloid cells, and myeloid-specific PD-1 knockout increased CD8 + T cells that expressed IFN-γ and IL-17 in a melanoma cancer model [ 142 ].…”