MicroRNA-155 Deficiency Suppresses Th17 Cell Differentiation and Improves Locomotor Recovery after Spinal Cord Injury.

Abstract

Spinal cord injury (SCI) is considered to be primarily associated with loss of motor function and leads to activate diverse cellular mechanisms in the central nervous system to attempt to repair the damaged spinal cord tissue. Mir-155 has been reported to be involved in both innate and adaptive immune responses. But the role of Mir-155 in spinal cord injury is still unknown. In our current study, Mir-155 deficiency displays increased myelin sparring and enhanced SC repair process. The number of T cells, B cells and neutrophils are all significantly lower in Mir-155(-/-) group than that in WT group after SCI. IL-17A-producing cells and the expression of IL-17A are markedly lower in Mir-155(-/-) mice than that in WT mice. We also found higher production of IL-17 by WT CD4(+) T cells than Mir-155(-/-) CD4(+) T cells in vitro. In our further DC-T cell coculture system, Mir-155 deficiency in DCs results in significantly less IL-17 production from T cells. Furthermore, the inhibited Th17 differentiation induced by Mir-155 deficiency is partly dependent on increased expression of SOCS1. In conclusion, our present work provides evidence to support the concept that Mir-155 deficiency suppresses Th17 cell differentiation and improves locomotor recovery after SCI.