Hyperbaric Oxygen Therapy Alleviates the Autoimmune Encephalomyelitis via the Reduction of IL-17a and GM-Csf Production of Autoreactive T Cells as Well as Boosting the Immunosuppressive IL-10 in the Central Nervous System Tissue Lesions.

Hsin-Ying Clair Chiou,Jiunn-Wei Wang,Shau-Ku Huang,Hui-Ru Kuo,Shu-Hung Huang,Deng-Chyang Wu,Ming-Hong Lin,Yu-Rui Huang,Su-Min Tsai,Szu-Chia Chen,Chih-Hsing Hung,Shih-Hsien Hsu,Chao-Hung Kuo

doi:10.3390/biomedicines9080943

Abstract

Multiple sclerosis (MS) is a chronic autoimmune disease mainly caused by autoreactive T cells, followed by neuronal demyelination and disabling paralysis. Hyperbaric oxygen therapy (HBOT) is usually an adjunct to therapy for the treatment of neurological disorders. However, it remains still controversial whether HBOT is an effective option for the treatment of MS. Experimental autoimmune encephalomyelitis (EAE) is a well-studied mouse model investigated for the MS pathogenesis and the efficacy of the therapeutic intervention. Both encephalitogenic Th1 and Th17 are pivotal T cell subsets immunopathogenically producing several disease-initiating/modifying cytokines in the central nervous system (CNS) lesions to further exacerbate/ameliorate the progression of EAE or MS. However, it remains unclear whether HBOT modulates the context of T helper cell subsets in CNS lesions. We employed EAE in the presence of HBOT to assess whether disease amelioration is attributed to alterations of CNS-infiltrating T cell subsets. Our results demonstrated that semi-therapeutic HBOT significantly alleviated the progression of EAE, at least, via the suppression of Th17 response, the downregulation of CD4 T helper cells expressing GM-CSF or TNF-α, and the boosting of immunomodulatory IL-4 or IL-10-expressed CD4 T cells in the CNS lesions. Conclusively, HBOT attenuated EAE through the modulation of T cell responses in an earlier stage.

Highlights

Multiple sclerosis (MS) is a chronic autoimmune and incurable disease of the central nervous system (CNS) manifested by neuronal demyelination and neuro-axonal damage and parenchymal mononuclear infiltration [1]
We found that the mean fluorescence index (MFI) of IFN-γ and IL-17A were notably diminished in CNS-infiltrating Th1 and Th17 cells of EAE mice receiving Hyperbaric Oxygen Therapy (HBOT) as compared to those of vehicle control, respectively (Figure 3E)
We demonstrated that semi-therapeutic HBOT alleviated the clinical manifestations and progression of MOG-immunized EAE in which mice received treatment in an earlier stage prior to the effector phase of disease

Summary

Introduction

Multiple sclerosis (MS) is a chronic autoimmune and incurable disease of the central nervous system (CNS) manifested by neuronal demyelination and neuro-axonal damage and parenchymal mononuclear infiltration [1]. The most common subtype of MS is relapsing-remitting multiple sclerosis (RRMS), in which the clinical symptoms of MS patients usually manifest as relapsing and remitting, in turn, mainly affecting the young adults towards the disabling diseases [2]. The immunopathology of MS is mainly attributed to the dysregulation of disease-initiating autoreactive T cells, producing higher amounts of pro-inflammatory cytokines as well as lower levels of immunosuppressive cytokines [1]. It is getting increasingly evident that multiple immune cell types participate in concert during the initiation and progression of MS [3]

Methods

Results

Discussion

Conclusion