Journal of Cell Science & Therapy
Open Access

Regional Neural Inputs Controlling Immune Cell Infiltration into the Central Nervous System

Michael Sean Pepper^{* *}Correspondence: Michael Sean Pepper, Department of Immunology, University of Pretoria, Pretoria, South Africa, Email:

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Description

It is well known that the Blood-Brain Barrier (BBB) in blood vessels strictly regulates the inflow of substances like proteins and cells from the bloodstream into the Central Nervous System (CNS), maintaining a homeostatic environment for nearby neurons and glia cells. This property differs from that in peripheral organs. Endothelial cells and the associated tight junctions created by claudins and occludins work with pericytes, microglial cells, macrophages, and astrocytes to form and maintain the BBB. Chronic neurodegenerative conditions like Parkinson's disease, Alzheimer's disease, and autoimmune diseases of the central nervous system are all known to be accompanied by BBB failure. Inflammatory cytokines have been linked to a malfunctioning BBB in a growing number of studies. TNF (tumour necrosis factor), IL-1, and IL-17A, for instance, have all been found to relax the BBB. The BBB is specifically known to be disrupted by IL-17A both in vitro and in vivo. According to Huppert et al., reactive oxygen species produced by NADPH oxidase and xanthine oxidase contribute to IL-17Ainduced BBB dysfunction by downregulating tight junction molecules and activating endothelial contractile machinery in vitro. In mice lacking in IL-17A, EAE is markedly inhibited. These mice, however, show a delayed onset, decreased maximum severity scores, improved histological alterations, and an early recovery. A further adoptive transfer paradigm showed that IL-17A produced from CD4+ T cells is essential for the production of EAE. In this model, helper T cells from Myelin Oligodendrocyte Glycoprotein (MOG) immunized mice were infused into nave recipients. Additionally, it was demonstrated that adoptive transfer of Th17 cells from ovalbumin-specific T cell receptor transgenic mice, which are unable to recognise CNS antigens, does not pass the BBB and migrate into the CNS, but that co-transfer of these Th17 cells with MOG-reactive Th17 cells results in the accumulation of both types of Th17 cells in the, which strongly suggests that antigen recognition of Th17 cells is required for severe disruption of the BBB. The type of antigenpresenting cells and site where antigen presentation occurs under physiological conditions are still unknown. Antigen presentation inside the CNS has suggested through observation that the infusion of ovalbumin peptide-loaded antigen-presenting cells into cerebrospinal fluids induces an accumulation of ovalbuminspecific Th17 cells in the CNS. Nevertheless, our findings imply that Th17 cells that express IL-17A and identify CNS antigens play a significant role in the BBB breach, possibly by reducing tight junction molecules. We talked about how inflammatory cytokines like IL-17A and BBB disruption are related in the previous section. The entry point for pathogenic CD4+ T lymphocytes into the CNS is the main topic of this section.

Early indicators of MS in patients typically include tingling and vision issues, which are followed as the disease advances by numerous neurological symptoms. White matter structures like the brainstem, the optic nerve, the cerebellum, and the lengthy motor and sensory tracts of the spinal cord are known to contain inflammatory sites in MS. This fact raises the possibility that particular CNS areas are more susceptible to autoimmune assaults. One theory suggests that these areas have higher concentrations of chemokines that attract pathogenic autoreactive T cells. CCL20, one of the many chemokines, is of particular relevance because it draws Th17 cells, which express CCR6, which is CCL20's receptor.

The choroid plexus, a specialised epithelial structure in the brain known to produce cerebrospinal fluids, expresses CCL20 constitutively, an effect that acts as an attractant for the first wave of CCR6+ Th17 cells. The complete Freund's adjuvant, however, which is frequently used to produce active immunization in animals but also induces systemic inflammation and has several side effects including fever, motor neuron dysfunction such as paralysis, and apoptosis, was employed to induce EAE in the same study. These side effects may alter the pathophysiological condition of the brain and spinal cords, leading to results that differ from those reached in the steady state. In an adoptive transfer model of mouse EAE, it has been discovered that the dorsal venules of the L5 spinal cord serve as a point of entry for MOG-reactive Th17 cells to gather into the CNS during steady state. The L5 gateway can be opened by gravity or electric stimulation of the soleus muscles, as previously mentioned.

Conclusion

The "gate theory," which we postulated in light of these findings, explains how localized brain stimulations direct immune cell infiltration into target organs by traversing gates situated at distinct blood venules. The gate theory's applicability to tissues besides the CNS is still being researched. It is anticipated that the ability to control these gates at specific locations in the body will have significant clinical benefits because closing them should reduce autoimmune inflammation in the target organ without causing systemic immune suppression, whereas opening them close to nearby tumours may increase the effectiveness of cancer immunotherapy. It takes a lot of work to pinpoint the precise molecular mechanisms for gating with such potential in medicine.