The Role of Th17 in Neuroimmune Disorders: Target for CAM Therapy. Part II

Abstract

Decades of research went into understanding the role that Th1 autoreactive T-cells play in neuroinflammation. Here we describe another effector population, the IL-17-producing T-helper lineage (Th17), which drives the inflammatory process. Through the recruitment of inflammatory infiltration neutrophils and the activation of matrix metalloproteinases, IL-17, a cytokine secreted by Th17 cells, contributes to blood-brain barrier breakdown and the subsequent attraction of macrophages and monocytes into the nervous system. The entry of cells along with the local production of inflammatory cytokines leads to myelin and axonal damage. This activation of the inflammatory response system is induced by different pathogenic factors, such as gut bacterial endotoxins resulting in progressive neurodegeneration by Th17 cells. Through the understanding of the role of bacterial endotoxins and other pathogenic factors in the induction of autoimmune diseases by Th17 cells, CAM practitioners will be able to design CAM therapies targeting IL-17 activity. Targeted therapy can restore the integrity of the intestinal and blood-brain barriers using probiotics, N-acetyl-cysteine, α-lipoic acid, resveratrol and others for their patients with autoimmunities, in particular those with neuroinflammation and neurodegeneration.

Figure 1

Proposed scheme of the induction by environmental factors of mucosal immune dysregulation and the production of inflammatory cytokines, resulting in the epithelial cell tight junction opening and the entry of bacterial and food antigens in the circulation and further activation of inflammatory cascade in the blood and in different tissues. CAM targets may include one or a combination of the following: inhibition of proinflammatory cytokines, inhibition of IL-1β binding to its receptor and inhibition of NF-κB activation.

Figure 2

The role of Th17 lymphocytes in the pathogenesis of inflammatory and neuroimmunological disorders. Environmental factors' induction of inflammatory response, production of cytokines and increase in the number of Th17 positive cells in circulation. Expression of IL-17 and IL-22 receptors on blood-brain barrier endothelial cells result in the binding of Th17 cells to BBB tight junctions. This disrupts the tight junctions, and the Th17 cells then transmigrate across the BBB, setting the stage for the killing of neurons by the release of granzyme B. CAM protocols may be used to block the inflammatory cascade induced by infection. Additionally, CAM therapies resulting in the repair of the BBB and the inhibition of lymphocyte transmigration can reduce neuro-inflammation.

Figure 3

Direct effect of bacterial antigens (LPS) on the production of substance P and its exacerbation of the early inflammatory response to neural cell antigens. CAM inhibition of NF-κB activation by microglia, astrocytes and macrophages may result in reduced neural cell damage.