Analysis of Infiltrating Immune Cells Following Intervertebral Disc Injury Reveals Recruitment of Gamma-Delta (γδ) T cells in Female Mice

Abstract

Inadequate repair of injured intervertebral discs (IVD) leads to degeneration and contributes to low back pain. Infiltrating immune cells into damaged musculoskeletal tissues are critical mediators of repair, yet little is known about their identities, roles, and temporal regulation following IVD injury. By analyzing longitudinal changes in gene expression, tissue morphology, and the dynamics of infiltrating immune cells following injury, we characterize sex-specific differences in immune cell populations and identify the involvement of previously unreported immune cell types, γδ and NKT cells. Cd3+Cd4-Cd8- T cells are the largest infiltrating lymphocyte population with injury, and we identified the presence of γδ T cells in this population in female mice specifically, and NKT cells in males. Injury-mediated IVD degeneration was prevalent in both sexes, but more severe in males. Sex-specific degeneration may be associated with the differential immune response since γδ T cells have potent anti-inflammatory roles and may mediate IVD repair.

The progression of neurovascular features and chemokine signatures of the intervertebral disc with degeneration

“…Recent work shows that the chronic NFκB activation in the caudal IVD produces a secretome that promote macrophage migration. 57 Our data here confirm that a degeneration-causing injury will upregulate a plethora of chemokines that will likely recruit multiple immune cell types 55 , concomitant with increasing neurovascular features. Future studies quantifying the presence of these immune cells would advance our understanding of a role for local versus systemic changes in modulating chemokine secretion, as well as key factors that govern the infiltration of these pain-associated features.…”

“…Many of the secreted chemokines found to be elevated may be associated with increased presence of infiltrating monocytes that may include macrophages, B-cells or T-cells. 55,56 Not surprisingly, the key angiogenic factor, VEGFA, was not elevated at any of the measured timepoints. VEGFA is critically expressed early following tissue repair promote early angiogenesis, 55 and by two-weeks following injury VEGFA has already exerted its effects as evidenced by robust vessel formation.…”

“…55,56 Not surprisingly, the key angiogenic factor, VEGFA, was not elevated at any of the measured timepoints. VEGFA is critically expressed early following tissue repair promote early angiogenesis, 55 and by two-weeks following injury VEGFA has already exerted its effects as evidenced by robust vessel formation. In this study, we are limited to chemokines differentially expressed between the injured and control IVDs; thereby, excluding chemokines that are more systemically expressed following puncture.…”

“…Many of the secreted chemokines found to be elevated may be associated with increased presence of infiltrating monocytes that may include macrophages, B-cells or T-cells. 55,56 Not surprisingly, the key angiogenic factor, VEGFA, was not elevated at any of the measured timepoints.…”

“…VEGFA is critically expressed early following tissue repair promote early angiogenesis, 55 and by twoweeks following injury VEGFA has already exerted its effects as evidenced by robust vessel formation.…”