Next Article in Journal
N-Acetyl-Aspartyl-Glutamate in Brain Health and Disease
Next Article in Special Issue
What Inhibits Natural Killers’ Performance in Tumour
Previous Article in Journal
Pseudomonas aeruginosa Triggered Exosomal Release of ADAM10 Mediates Proteolytic Cleavage in Trans
Previous Article in Special Issue
Molecular Determinants and Specificity of mRNA with Alternatively-Spliced UPF1 Isoforms, Influenced by an Insertion in the ‘Regulatory Loop’
Article

Targeting Interleukin-10 Restores Graft Microvascular Supply and Airway Epithelium in Rejecting Allografts

1
Transplantation Research and Innovation Department, Organ Transplant Centre of Excellence, King Faisal Specialist Hospital and Research Centre, Riyadh 12713, Saudi Arabia
2
Comparative Medicine Department, King Faisal Specialist Hospital and Research Centre, Riyadh 12713, Saudi Arabia
3
College of Medicine, Alfaisal University, Riyadh 12713, Saudi Arabia
*
Author to whom correspondence should be addressed.
Academic Editor: Daniela Novick
Int. J. Mol. Sci. 2022, 23(3), 1269; https://doi.org/10.3390/ijms23031269
Received: 30 November 2021 / Revised: 9 January 2022 / Accepted: 12 January 2022 / Published: 23 January 2022
(This article belongs to the Special Issue Manipulating Immune Tolerance with Cellular Therapies)
Interleukin-10 (IL-10) is a vital regulatory cytokine, which plays a constructive role in maintaining immune tolerance during an alloimmune inflammation. Our previous study highlighted that IL-10 mediated immunosuppression established the immune tolerance phase and thereby modulated both microvascular and epithelial integrity, which affected inflammation-associated graft malfunctioning and sub-epithelial fibrosis in rejecting allografts. Here, we further investigated the reparative effects of IL-10 on microvasculature and epithelium in a mouse model of airway transplantation. To investigate the IL-10 mediated microvascular and epithelial repair, we depleted and reconstituted IL-10, and monitored graft microvasculature, airway epithelium, and associated repair proteins. Our data demonstrated that both untreated control allografts and IL-10 (−) allografts showed a significant early (d6) increase in microvascular leakiness, drop-in tissue oxygenation, blood perfusion, and denuded airway epithelium, which is associated with loss of adhesion protein Fascin-1 and β-catenin on vascular endothelial cells at d10 post-transplantation. However, IL-10 (+) promotes early microvascular and airway epithelial repair, and a proportional increase in endothelial Fascin-1, and β-catenin at d10 post-transplantation. Moreover, airway epithelial cells also express a significantly higher expression of FOXJ1 and β-catenin in syngrafts and IL-10 (+) allografts as compared to IL-10 (−) and untreated controls at d10 post-transplantation. Collectively, these findings demonstrated that IL-10 mediated microvascular and epithelial changes are associated with the expression of FOXJ1, β-catenin, and Fascin-1 proteins on the airway epithelial and vascular endothelial cells, respectively. These findings establish a potential reparative modulation of IL-10 associated microvascular and epithelial repair, which could provide a vital therapeutic strategy to facilitate graft repair in clinical settings. View Full-Text
Keywords: interleukin-10; microvascular leakiness; airway epithelium interleukin-10; microvascular leakiness; airway epithelium
Show Figures

Figure 1

MDPI and ACS Style

Kazmi, S.; Khan, M.A.; Shamma, T.; Altuhami, A.; Ahmed, H.A.; Mohammed Assiri, A.; Broering, D.C. Targeting Interleukin-10 Restores Graft Microvascular Supply and Airway Epithelium in Rejecting Allografts. Int. J. Mol. Sci. 2022, 23, 1269. https://doi.org/10.3390/ijms23031269

AMA Style

Kazmi S, Khan MA, Shamma T, Altuhami A, Ahmed HA, Mohammed Assiri A, Broering DC. Targeting Interleukin-10 Restores Graft Microvascular Supply and Airway Epithelium in Rejecting Allografts. International Journal of Molecular Sciences. 2022; 23(3):1269. https://doi.org/10.3390/ijms23031269

Chicago/Turabian Style

Kazmi, Shadab, Mohammad A. Khan, Talal Shamma, Abdullah Altuhami, Hala A. Ahmed, Abdullah Mohammed Assiri, and Dieter C. Broering. 2022. "Targeting Interleukin-10 Restores Graft Microvascular Supply and Airway Epithelium in Rejecting Allografts" International Journal of Molecular Sciences 23, no. 3: 1269. https://doi.org/10.3390/ijms23031269

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop