Dynamics of Intraocular IFN-γ, IL-17 and IL-10-Producing Cell Populations during Relapsing and Monophasic Rat Experimental Autoimmune Uveitis

Purpose: A small molecular compound, aminooxy-acetic acid (AOA), has been shown to modulate experimental autoimmune encephalomyelitis (EAE). The current study was designed to investigate whether AOA has a similar effect on the development of experimental autoimmune uveitis (EAU) and to further explore underlying mechanisms of this drug. Methods: EAU was induced in C57BL/6J mice by immunization with interphotoreceptor retinoid-binding protein peptide 651-670 (IRBP 651-670). AOA (500μg or 750μg) or vehicle was administered by intraperitoneal injection from day 10 to 14 after EAU induction. The severity was assessed by clinical and histological scores. The integrity of the blood retinal barrier was detected with Evans Blue. Frequencies of splenic Th1, Th17 and Foxp3+ Treg cells were examined by flow cytometry. The production of cytokines was tested by ELISA. The mRNA expression of IL-17, IFN-γ and IL-10 was detected by RT-PCR. The expression of p-Stat1 and NF-κB was detected by Western Blotting. Results: AOA was found to markedly inhibit the severity of EAU, as determined by clinical and histopathological examinations. AOA can relieve the leakage of blood retinal barrier (BRB). Functional studies found a decreased frequency of Th1 and Th17 cells and an increased frequency of Treg cells in EAU mice as compared with controls. Further studies showed that AOA not only downregulated the production of the proinflammatory cytokines including IFN-γ and IL-17 but also upregulated the expression of an anti-inflammatory cytokine such as IL-10, which might be caused by inhibiting the expressions of p-Stat1 and NF-κB. Conclusion: This study shows that AOA inhibits the severity and development of EAU by modulating the balance between regulatory and pathogenic lymphocyte subsets.

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IFN-γ up-regulation of IL-12 beta 2 receptor is associated with experimental autoimmune uveitis susceptible B10.A mice, but not in EAU resistant BALB/c mice

Journal of Neuroimmunology ◽

10.1016/s0165-5728(03)00071-7 ◽

2003 ◽

Vol 137 (1-2) ◽

pp. 154-163 ◽

Cited By ~ 5

Author(s):

Y Wu

Keyword(s):

Experimental Autoimmune Uveitis ◽

Autoimmune Uveitis ◽

Ifn Γ ◽

Beta 2 ◽

Experimental Autoimmune

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TMP778, a selective inhibitor of RORγt, suppresses experimental autoimmune uveitis development, but affects both Th17 and Th1 cell populations

European Journal of Immunology ◽

10.1002/eji.201747029 ◽

2018 ◽

Vol 48 (11) ◽

pp. 1810-1816 ◽

Cited By ~ 4

Author(s):

Cancan Lyu ◽

So Jin Bing ◽

Wambui S. Wandu ◽

Biying Xu ◽

Guangpu Shi ◽

...

Keyword(s):

Selective Inhibitor ◽

Cell Populations ◽

Experimental Autoimmune Uveitis ◽

Th1 Cell ◽

Autoimmune Uveitis ◽

Experimental Autoimmune

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Functionally distinct IFN‐γ + IL‐17A + Th cells in experimental autoimmune uveitis: T‐cell heterogeneity, migration, and steroid response

European Journal of Immunology ◽

10.1002/eji.202048616 ◽

2020 ◽

Vol 50 (12) ◽

pp. 1941-1951

Author(s):

Yi‐Hsing Chen ◽

Malihe Eskandarpour ◽

Aurelia Gondrand ◽

Xiaozhe Zhang ◽

Renyang Gu ◽

...

Keyword(s):

T Cell ◽

Cell Heterogeneity ◽

Experimental Autoimmune Uveitis ◽

Th Cells ◽

Autoimmune Uveitis ◽

Steroid Response ◽

Ifn Γ ◽

Experimental Autoimmune

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Overexpressing Kallistatin Aggravates Experimental Autoimmune Uveitis Through Promoting Th17 Differentiation

Frontiers in Immunology ◽

10.3389/fimmu.2021.756423 ◽

2021 ◽

Vol 12 ◽

Author(s):

Nu Chen ◽

Shuang Chen ◽

Zhihui Zhang ◽

Xuexue Cui ◽

Lingzi Wu ◽

...

Keyword(s):

T Cells ◽

Binding Protein ◽

Wild Type ◽

Experimental Autoimmune Uveitis ◽

Autoimmune Uveitis ◽

Interphotoreceptor Retinoid Binding Protein ◽

Infectious Uveitis ◽

Ifn Γ ◽

Th17 Differentiation ◽

Experimental Autoimmune

Kallistatin or kallikrein-binding protein (KBP) has been reported to regulate angiogenesis, inflammation and tumor progression. Autoimmune uveitis is a common, sight-threatening inflammatory intraocular disease. However, the roles of kallistatin in autoimmunity and autoreactive T cells are poorly investigated. Compared to non-uveitis controls, we found that plasma levels of kallistatin were significantly upregulated in patients with Vogt-Koyanagi-Harada (VKH) disease, one of the non-infectious uveitis. Using an experimental autoimmune uveitis (EAU) model induced by human interphotoreceptor retinoid-binding protein peptide 651-670 (hIRBP651-670), we examined the effects of kallistatin on the pathogenesis of autoimmune diseases. Compared to wild type (WT) mice, kallistatin transgenic (KS) mice developed severe uveitis with dominant Th17 infiltrates in the eye. In addition, the proliferative antigen-specific T cells isolated from KS EAU mice produced increased levels of IL-17A, but not IFN-γ or IL-10 cytokines. Moreover, splenic CD4+ T cells from naïve KS mice expressed higher levels of Il17a mRNA compared to WT naïve mice. Under Th17 polarization conditions, KS mice exhibited enhanced differentiation of naïve CD4+ T cells into Th17 cells compared to WT controls. Together, our results indicate that kallistatin promotes Th17 differentiation and is a key regulator of aggravating autoinflammation in EAU. Targeting kallistatin might be a potential to treat autoimmune disease.

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