Substance P Activates The Epidermal Dendritic T Cells To Promote Wound Healing By Producing Ngf
Guo-You ZHANG, Yi-Xuan ZHAO, Qing-Feng LI, Lian ZHU.
Shanghai Ninth People’s Hospital, Shanghai, China.
BACKGROUND: Accumulating evidences have show that neuro-immuno-endocrine modulation plays an essential role in the wound healing. However, the underlying mechanisms behind this axis still remain unknown. Here, the aim of this study is to clarify the role of substance P on the dendritic epidermal γδ T cells (DETC) in the wound healing. METHODS: The epidermal dendritic epidermal T cells (γδT cells), which were isolated and then further sorted by FACS, 7-17 T cells and PAM212 cell line were used here. After treatment by substance P, a series of methods (ELISA, CCK8 assay, RT-PCR, western blotting, scratch wound healing) were applied to analyze. RESULTS: Neurokinin receptors (NKRs) were not only expressed in skin γδT cells, but also located with differently subtypes in epidermal and dermal skin γδT cells. Following substance P treatment, it rapidly activates γδT cells and leads to an increase CD69 expression, and NGF production, and to changes in DETC morphology (p<0.05). Furthermore, we find that TCR activation is necessary for substance P-induced NGF production in γδT cells. In addition, substance P-activated γδT cells not only enhance keratinocytes migration, but also increase enhance keratinocytes proliferation (p<0.05), which inhibited by NK1R inhibitor and NGF inhibitory antibody. Finally, we demonstrated that substance P-induced NGF production by γδT cells does require ERK1/2 activation (p<0.05). CONCLUSIONS: Here, we uncover a novel mechanism of neuro-immuno-endocrine modulation based on the fact that substance P can activate γδT cells induces NGF production. These findings suggest that it could be used in the therapeutically in the clinical wound treatment.
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