Recruitment of γδ T cells to the lesion via the CCL2/CCR2 signaling after spinal cord injury

Background Immune cell infiltration and neuroinflammation are heavily associated with spinal cord injury (SCI). C-C motif chemokine ligand 2/C-C chemokine receptor type 2 (CCL2/CCR2) axis has been identified as a critical role player during the invasion of immune cells to lesions in many diseases. gamma delta T cells, a subgroup of T cells, manage the course of inflammation response in various diseases; however, it remains unknown whether gamma delta T cells are recruited to injury site through CCL2/CCR2 signaling and exert the regulation effect on neuroinflammation after SCI. Methods Basso Mouse Scale (BMS), regularity index, cadence, max contact area, and motor-evoked potential testing (MEP) were measured to determine the neurological function recovery after spinal cord injury. Nissl staining was performed to identify the number of surviving motor neurons at lesion epicenter. Immunofluorescence, Western blot, enzyme-linked immunosorbent assays (ELISA), and quantitative real-time polymerase chain reaction (QRT-PCR) also were employed to evaluate the expression of associated proteins and genes. Results In this study, we demonstrated that TCR delta(-/-) mice present improved neurological recovery after SCI. gamma delta T cell recruitment to the SCI site was significantly reduced and motor functional improvement enhanced in CCL2(-/-) and CCR2(-/-) mouse strains. Furthermore, reconstitution of TCR delta(-/-) mice with gamma delta T cells extracted from CCR2(-/-) mice also showed similar results to CCL2 and CCR2 deficient mice. Conclusions In conclusion, gamma delta T cell recruitment to SCI site promotes inflammatory response and exacerbates neurological impairment. CCL2/CCR2 signaling is a vital recruitment mechanism of gamma delta T cells to the SCI site, and it may be taken as a novel therapeutic target for future SCI.

Automated summary

This study demonstrates that γδ T cells are recruited to the site of spinal cord injury through CCL2/CCR2 signaling, exacerbating inflammatory response and worsening neurological impairment. This mechanism could be a potential therapeutic target for future SCI treatment.