Th17-Related Cytokines as Potential Discriminatory Markers between Neuromyelitis Optica (Devic’s Disease) and Multiple Sclerosis—A Review

Abstract

Multiple sclerosis (MS) and Devic’s disease (NMO; neuromyelitis optica) are autoimmune, inflammatory diseases of the central nervous system (CNS), the etiology of which remains unclear. It is a serious limitation in the treatment of these diseases. The resemblance of the clinical pictures of these two conditions generates a partial possibility of introducing similar treatment, but on the other hand, a high risk of misdiagnosis. Therefore, a better understanding and comparative characterization of the immunopathogenic mechanisms of each of these diseases are essential to improve their discriminatory diagnosis and more effective treatment. In this review, special attention is given to Th17 cells and Th17-related cytokines in the context of their potential usefulness as discriminatory markers for MS and NMO. The discussed results emphasize the role of Th17 immune response in both MS and NMO pathogenesis, which, however, cannot be considered without taking into account the broader perspective of immune response mechanisms.

Biomarkers in autoimmune diseases of the central nervous system

“…Interleukin-17A (IL-17A) is an effective proinflammatory cytokine produced by Th17 cells and IL-17-secreting CD8+T cells ( 85 ). It promotes the pathophysiology of autoimmune diseases and may mediate delayed inflammation by inducing neutrophils and monocytes to recruit chemokines at inflammatory sites ( 85 ).…”

“…Interleukin-17A (IL-17A) is an effective proinflammatory cytokine produced by Th17 cells and IL-17-secreting CD8+T cells ( 85 ). It promotes the pathophysiology of autoimmune diseases and may mediate delayed inflammation by inducing neutrophils and monocytes to recruit chemokines at inflammatory sites ( 85 ). A recent study has shown that IL-17 impairs myelin regeneration and promotes myelin damage through oligodendrocyte/myelin injury mediated by increasing voltage-gated K+ channel 1 ( 86 ).…”

Neuromyelitis Optica Spectrum Disorder: From Basic Research to Clinical Perspectives

“…Naive T-helper cells differentiate into a new lineage called Th17 and have the capacity to produce large amounts of IL-17, a cytokine linked to autoimmune diseases [ 67 , 106 ]. IL-6 signaling involving Th17 cells and Th17-associated cytokines may play a crucial role in the pathogenesis of NMOSD ( Figure 1 ) [ 66 , 107 , 108 , 109 , 110 ]. Apart from IL-17, Th17-cell differentiation may be induced by IL-6, IL-23, and transforming growth factor β1 [ 111 , 112 ].…”

“…Third, the coinjection of AQP4-IgG antibodies and complement can activate the complement system in rats but not in mice and may lead to underestimation of the complement inhibitory function. Finally, EAE models in rats are Th1-cell-mediated, whereas AQP4-specific T cells in NMO reportedly show a preferential involvement of Th17/Th2 lymphocytes including IL-6- and Th17-polarizing cytokine interactions [ 65 , 108 , 178 ].…”

Exosomes with FOXP3 from gene-modified dendritic cells ameliorate the development of EAE by regulating the balance of Th/Treg

“…These demonstrations indicated that FOXP3-EXOs treatment could efficiently ameliorate the development of EAE by, at least partly, regulating the immune homeostasis of Th/Treg. It is well-established that Th1 and Th17 cells not only represented a major initiator but was also a participant in the pathogenesis and progression of MS as well as its animal model-EAE: 1) In MS, raised proportion of Th1 and Th17 cells in the peripheral blood and increased concentrations of Th1-and Th17-related cytokines such us IFN-γ, TNF-α, IL-6, IL-17, IL-21, IL-22, and IL-23 in the serum had been mentioned in numerous previous studies [2,9,29]. 2) MOG-specific-Th1 and Th17 cells could induce typical adoptive transfer EAE [30].…”