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

Abstract

CD4+ effector cells, based on cytokine production, nuclear receptors and signaling pathways, have been categorized into four subsets. T-helper-1 cells produce IFN-γ, TNF-β, lymphotoxin and IL-10; T-helper-2 cells produce IL-4, IL-5, IL-10, IL-13, IL-21 and IL-31; T-helper-3, or regulatory T-cells, produce IL-10, TGF-β and IL-35; and the recently discovered T-helper-17 cell produces IL-17, IL-17A, IL-17F, IL-21, IL-26 and CCL20. By producing IL-17 and other signaling molecules, Th17 contributes to the pathogenesis of multiple autoimmune diseases including allergic inflammation, rheumatoid arthritis, autoimmune gastritis, inflammatory bowel disease, psoriasis and multiple sclerosis. In this article, we review the differential regulation of inflammation in different tissues with a major emphasis on enhancement of neuroinflammation by local production of IL-17 in the brain. By understanding the role of pathogenic factors in the induction of autoimmune diseases by Th17 cells, CAM practitioners will be able to design CAM therapies targeting Th17 and associated cytokine activities and signaling pathways to repair the intestinal and blood-brain barriers for their patients with autoimmunities, in particular, those with neuroinflammation and neurodegeneration.

Th17-skewed immune response and cluster of differentiation 40 ligand expression in canine steroid-responsive meningitis-arteritis, a large animal model for neutrophilic meningitis

“…IL-17 is a pro-inflammatory cytokine secreted primarily by activated T cells [23, 24, 29, 30, 58, 59], although it is also produced by neutrophils [24], eosinophils [25], and monocytes [26]. IL-17 acts on the IL-17 receptor (IL-17R) expressed on the cells of all the tissues examined to date [27].…”

Reference Values for a Panel of Cytokinergic and Regulatory Lymphocyte Subpopulations

“…All these sub-classes are believed to play an important role in chronic immune dysregulations and are included in diagnostic cytofluorimetric lymphocyte panels used for such conditions (4748), including neuro-immune dysregulations (495051). …”

Leuprolide Acetate Inhibits Spinal Cord Inflammatory Response in Experimental Autoimmune Encephalomyelitis by Suppressing NF-κB Activation

“…Interestingly, IL-17 synergizes with these two previously analyzed inflammatory cytokines, IL-1β and TNF-α, to further induce cytokine expression [37]. It is known that IL-17 is among the most highly expressed genes in MS lesions [38].…”