Roles of Treg/Th17 Cell Imbalance and Neuronal Damage in the Visual Dysfunction Observed in Experimental Autoimmune Optic Neuritis Chronologically

Abstract

Optic neuritis associated with multiple sclerosis and its animal model, experimental autoimmune optic neuritis (EAON), is characterized by inflammation, T cell activation, demyelination, and neuronal damage, which might induce permanent vision loss. Elucidating the chronological relationship among the features is critical for treatment of demyelinating optic neuritis. EAON was induced in C57BL/6 mice immunized with myelin oligodendrocyte glycoprotein subcutaneously, and visual function was assessed by flash-visual evoked potential (F-VEP) at days 7, 11, 14, 19, 23, 28 post-immunization. Retinal ganglion cell (RGC) apoptosis was measured by terminal-deoxynucleotidyl transferase-mediated nick-end labeling. Demyelination and axonal damage were verified with myelin basic protein (MBP) and β-amyloid precursor protein staining, respectively. Real-time polymerase chain reaction quantified IL-17, IL-1β, TGF-β, FoxP3, IL-6, and IL-10 mRNA expression in the optic nerve, as well as FoxP3 and IL-17 staining. Systemic changes of Th17 and Treg cells were tested by flow cytometry in spleen. F-VEP latency was prolonged at 11 days and peaked at 23 days commensurate with demyelination. However, F-VEP amplitude was reduced at 11 days, preceding axon damage, and was exacerbated at 23 days when a peak in RGC apoptosis was detected. Th17 cells up-regulated as early as 7 days and peaked at 11 days, while Treg cells down-regulated inversely compared to Th17 cells change as verified by IL-17 and FoxP3 expression; spleen cell samples were slightly different, demonstrating marked changed at 14 days. Treg/Th17 cell imbalance in the optic nerve precedes and may initiate neuronal damage of axons and RGCs. These changes are commensurate with the appearances of visual dysfunction reflected in F-VEP and hence may offer a novel therapeutic avenue for vision preservation.

TH17 cells mediate inflammation in a novel model of spontaneous experimental autoimmune lacrimal keratoconjunctivitis with neural damage

“…IL-17 with iNOS also induces the damage of corneal nerve (Figure 8). 27–29 Consistent with these findings, we found an increase in inflammatory cytokines in the tears of patients with DED. In particular, IL-17, as well as TNFα is increased in patients with and without Sjögren’s syndrome.…”

Comparison of T Helper Cell Patterns in Primary Open-Angle Glaucoma and Normal-Pressure Glaucoma

“…Balanced responses of both pro- and anti-inflammatory Th cells are essential to prevent an immune response from turning into autoimmune disease. Recently, imbalances have been reported to be responsible for some autoimmune diseases, such as multiple sclerosis and type 1 diabetes, which are also associated with HSP60 [ 20 , 21 ]. Therefore, in this study, after evaluating the levels of HSP60 and its antibody in our POAG and NPG patients, we evaluated the percentages of the main Th cells involved in pro-inflammatory and anti-inflammatory responses, attempting to explain the discrepancy with regard to the presence of HSP60 and higher titers of HSP60 antibody in NPG patients compared to POAG patients.…”

MiR-384 Regulates the Th17/Treg Ratio during Experimental Autoimmune Encephalomyelitis Pathogenesis

“…An imbalance between IL-17-producing CD4 + T helper (Th17) cells, which express the lineage-specific transcription factor, RORγt (Ciofani et al, 2012), and activated regulatory T (Treg) cells expressing Foxp3 (Gerriets et al, 2016) has a significant role in induction of inflammatory immune responses (Korn et al, 2009; Liu Y. et al, 2015; Zhu et al, 2016). This Th17/Treg imbalance is associated with various autoimmune and inflammatory diseases, including MS (Tzartos et al, 2008; Jamshidian et al, 2013, 2015; Lochner et al, 2015).…”