IL-15 Enhances Activation and IGF-1 Production of Dendritic Epidermal T Cells to Promote Wound Healing in Diabetic Mice.

Yangping Wang,Yang Bai,Gaoxing Luo,Meixi Liu,Yufeng Jiang,Zhinan Yin,Jun Wu,Zhongyang Liu,Xiaohong Hu,Yashu Li,Rupeng Wang,Guangping Liang,Weifeng He,Jian Chen,Jianlei Hao,Xiaorong Zhang

doi:10.3389/fimmu.2017.01557

Abstract

Altered homeostasis and dysfunction of dendritic epidermal T cells (DETCs) contribute to abnormal diabetic wound healing. IL-15 plays important roles in survival and activation of T lymphocytes. Recently, reduction of epidermal IL-15 has been reported as an important mechanism for abnormal DETC homeostasis in streptozotocin -induced diabetic animals. However, the role of IL-15 in impaired diabetic wound healing remains unknown. Here, we found that, through rescuing the insufficient activation of DETCs, IL-15 increased IGF-1 production by DETCs and thereby promoted diabetic skin wound repair. Regulation of IGF-1 in DETCs by IL-15 was partly dependent on the mTOR pathway. In addition, expression of IL-15 and IGF-1 were positively correlated in wounded epidermis. Together, our data indicated that IL-15 enhanced IGF-1 production by DETCs to promoting diabetic wound repair, suggesting IL-15 as a potential therapeutic agent for managing diabetic wound healing.

Highlights

Dendritic epidermal T cells (DETCs) uniformly express an invariant Vγ5Vδ1 TCR [1] and reside in murine epidermis
Our previous study reported that diabetic mice exhibited decreased levels of IGF-1 and a substantial reduction of DETCs in both intact and wounded epidermis compared with vehicle-treated controls [9]
We showed that rapamycin notably inhibited IGF-1 production in DETCs, which were freshly isolated from wound area by MACS, in the presence of rIL-15 plus anti-CD3 stimulation in vitro (Figure 4B), suggesting that mTOR was involved in IL-15-mediated upregulation of IGF-1 production from DETCs

Summary

Introduction

Dendritic epidermal T cells (DETCs) uniformly express an invariant Vγ5Vδ1 TCR [1] and reside in murine epidermis. DETCs are required for efficient wound repair, in which IGF-1 as one of key factors plays critical roles [2,3,4,5]. The altered homeostasis and dysfunctions of DETCs contribute to impaired diabetic wound healing [6, 7]. A notable reduction of epidermal IGF-1 production, which is majorly secreted by DETCs, has been reported in streptozotocin (STZ)-induced diabetic animals [8]. Addition of rIGF-1 onto wound bed significantly improves defects of diabetic wound healing [9,10,11,12]. Reduction of IGF-1 by DETCs contributes to defective diabetic wound repair. The underlying mechanisms for impaired IGF-1 production by DETCs in diabetes remain unknown

Methods

Results

Conclusion