A. S. Kimball1, A. Boniakowski1, A. Joshi1, M. Schaller1, R. Allen1, P. Henke1, I. Maillard1, S. Kunkel1, K. Gallagher1 1University Of Michigan,Ann Arbor, MI, USA
Introduction: For the past century, the study of wound healing has focused mainly on the role of the innate immune system in maintaining tissue homeostasis. Up to this point, there have been few studies looking directly at adaptive immune cells and their role in promoting tissue repair. In this study, we sought to quantify the presence of T-cells in wounds over time and to evaluate their effects on wound healing by blocking a well-described T-cell signaling pathway.
Methods: C57BL/6 mice were obtained for general wound healing studies. DNMAMLf/f CD4-Cre+/- mice were obtained to evaluate wound healing in the setting of canonical Notch signaling blockade in CD4+ cells. 4mm punch biopsies were created on the mid-backs of the mice and wound healing was monitored daily using NIH ImageJ software. Wounds were harvested at various time-points for cell isolation and analysis. CD3+ cell volumes were calculated over-time post-injury using analytical flow cytometry.
Results: CD3+ T-Cells are present and dynamic in wounds over-time post-injury, representing ~4% of live cells at day 2 and ~6% of the live cells at day 6. Given the two peaks of T-cell presence in the inflammatory and proliferative phases of wound healing, we sought to probe the relevance of these cells by blocking the well described Notch signaling pathway in CD4+ cells. Wound healing was evaluated in DNMAMLf/f CD4-Cre+ vs. Cre- mice and this demonstrated significantly delayed wound healing in those mice with impeded Notch signaling.
Conclusion: Contrary to popular dogma, the adaptive immune system plays a not-insignificant role in wound healing and further studies are needed to evaluate the role of T-cells and Notch signaling. These findings are consistent with the impaired wound healing seen in immunocompromised patients and represents an exciting new area of future research.
