Mechanism of T helper cell for demyelinated optic neuritis
10.3760/cma.j.issn.2095-0160.2014.05.006
- VernacularTitle:辅助性T细胞在脱髓鞘性视神经炎发病中的作用
- Author:
Jing, PANG
;
Yuanyuan, LIU
;
Hua, YAN
- Publication Type:Journal Article
- Keywords:
Optic neuritis;
Immunoregulation;
Th17 cell;
Treg cell
- From:Chinese Journal of Experimental Ophthalmology
2014;32(5):408-414
- CountryChina
- Language:Chinese
-
Abstract:
Background Optic neuritis is one of the common clinical neuro-ophthalmic diseases.Recurrent optic neuritis can cause irreversible axonal damage and visual impairment,and no prevention method is effective up to now.Its pathogenesis is considered to be associated with the body's immune imbalance.Objective This proposal tried to establish experimental autoimmune encephalomyelitis (EAE) and explore the immunomodulatory effects of T helper (Treg),Th17 cell in the model of optic neuritis.Make the immune mechanism of demyelinating optic neuritis clear.Methods EAE model was established to observe the clinical symptoms and visual electrophysiological changes of optical neuritis in mice;hematoxylin-eosin staining to observe the histological changes in the mouse models of EAE; immunohistochemical staining to detect optic nerve axon damage markers β-amyloid peptide precurso (β-APP) protein expression quantity changes;reverse transcription PCR (RT-PCR) to detect the dynamic expression of forkhead/winged helix transcription factor p3 (Foxp3),transforming growth factor-β (TGF-β),interleukin-1β (IL-1β),IL-17,IL-10 in optic nerve tissue.Results After immunization 11 days,neurological symptoms of EAE mice started to appear,hematoxylin-eosin staining showed optic nerve tissue infiltration of inflammatory cytokines; immunohistochemical staining showed enhancement of axonal injury markers β-APP positive staining; flash visual evoked potential(F-VEP) test showed 7,11,14,19,23,28 days,compared with the normal mice,P1 prepatents of model group were prolonged after modeling,the differences were statistically significant (t =4.487,15.203,16.364,11.540,11.959,16.163,all at P＜0.05).When 7 days after modeling,the difference of N1-P1 amplitude between normal group and model group was no statistical significance (t =-0.992,P =0.378); while 11,14,19,23,28 days after modeling,compared with normal mice,N1-P1 amplitudes of model mice were significantly lower,the differences were statistically significant(all at P＜ 0.05).The expressions of TGF-β,IL-1β,IL-17,Foxp3,IL-10 mRNA among different time points had stastistie significant differences (F =12.721,15.015,14.343,69.374,68.290,all at P =0.000),compared with the normal group,when 11 days,14 days after modeling,TGF-β mRNA levels were significantly increased ; 19 days,23 days after modeling,IL-1β mRNA levels were significantly increased;7 days,11 days after modeling,IL-17 mRNA levels were significantly increased ;7,11,14,19,23,28 days after modeling,Foxp3 mRNA levels were significantly lower; 19,23,28 days after modeling,IL-10 mRNA levels were significantly lower,the difference were statistically significant (all at P＜ 0.05).Conclusions Th17 cells launch demyelinating optic neuritis immune injury,and Th1 subgroup performs the function of maintaining inflammatory lesions,Treg cell subgroup is abnormal much earlier than that of the Th2 subgroup.The imbalance of Th17/Treg cell may be involved in the pathogenesis of demyelinating optic neuritis.
