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.

Keywords: annulus fibrosus; auto-immune response; immune privilege; intervertebral disc; nucleus pulposus.

Figure 1

Development of the intervertebral disc (IVD). A. Sclerotome condenses around the notochord to form the vertebrae and the putative annulus fibrosus (AF) while the notochordal is contracted from the vertebral body and expands into the area of the future nucleus pulposus (NP) area. B. The notochordal is compressed and becomes entrapped in the surrounding dense ring of sclerotome-derived connective tissue, which develops to the AF. C. Endochondral bone formation occurs in the sclerotome vertebra and expands to become bony vertebra. Hyaline cartilage adjacent to the IVD is maintained and develops to the cartilaginous endplate (CEP).

Figure 2

Schematic representation for the immune privilege of the intervertebral disc (IVD). A. In normal IVD, the blood-NP barrier (BNB) is composed of the annulus fibrosus (AF), the cartilaginous endplate (CEP) and immunosuppressive molecular factors. The BNB isolates the central nucleus pulposus (NP) from the immune system of the host and provides fundamental basis for the homeostasis of the IVD. B. The breakdown of the BNB leads to the exposure of the NP and induces auto-immune response. This effect causes immunocytes activation and inflammatory factors infiltration, contributing to the immune stress of the nerve root with vascularization and neurotization.