The Immune Privilege of the Intervertebral Disc: Implications for Intervertebral Disc Degeneration Treatment

Abstract

The intervertebral disc (IVD) is the largest avascular organ of the body. It is composed of three parts: the nucleus pulposus (NP), the annulus fibrosus (AF) and the cartilaginous endplate (CEP). The central NP is surrounded by the AF and sandwiched by the two CEPs ever since its formation. This unique structure isolates the NP from the immune system of the host. Additionally, molecular factors expressed in IVD have been shown inhibitive effect on immune cells and cytokines infiltration. Therefore, the IVD has been identified as an immune privilege organ. The steady state of immune privilege is fundamental to the homeostasis of the IVD. The AF and the CEP, along with the immunosuppressive molecular factors are defined as the blood-NP barrier (BNB), which establishes a strong barrier to isolate the NP from the host immune system. When the BNB is damaged, the auto-immune response of the NP occurs with various downstream cascade reactions. This effect plays an important role in the whole process of IVD degeneration and related complications, such as herniation, sciatica and spontaneous herniated NP regression. Taken together, an enhanced understanding of the immune privilege of the IVD could provide new targets for the treatment of symptomatic IVD disease. However, the underlying mechanism above is still not fully clarified. Accordingly, the current study will extensively review and discuss studies regarding the immune privilege of the IVD.

DIPPER, a spatiotemporal proteomics atlas of human intervertebral discs for exploring ageing and degeneration dynamics

“…Interestingly, these modules all showed a tendency for convex patterns with upward expression toward the OAF regions, in both lateral and anteroposterior directions, in all levels, combined or separated (Figure 3F-H; Figure 3-figure supplement 3B-D). The higher proportions of ECM, muscle contraction and immune system proteins in the OAF are consistent with the contractile function of the AF (Nakai et al, 2016), and with the NP being avascular and "immune-privileged" in a young homeostatic environment (Sun et al, 2020).…”

DIPPER: a spatiotemporal proteomics atlas of human intervertebral discs for exploring ageing and degeneration dynamics

“…Interestingly, these modules all showed a tendency for convex patterns with upward expression toward the OAF regions, in both lateral and anteroposterior directions, in all levels, combined or separated ( Figure 3F-H; Supplemental S8B-D). The higher proportions of ECM, muscle contraction and immune system proteins in the OAF are consistent with the contractile function of the AF (Nakai et al, 2016), and with the NP being avascular and "immune-privileged" in a young homeostatic environment (Sun et al, 2020).…”

Intervertebral Disc and Adipokine Leptin—Loves Me, Loves Me Not

“…However, the disappearance of notochordal cells in human IVD is a matter of debate, since a considerable proportion of cells within NP of adults display notochord-like phenotype [ 15 ]. Animal studies found that both NP cells and notochordal cells originate from the embryonic notochord [ 14 ].…”