Resolution of uveitis

Wildner, Gerhild; Diedrichs-Möhring, Maria

doi:10.1007/s00281-019-00758-z

“…Autoimmune uveitis (AU) has been widely considered as one of the ocular inflammatory disorders that cause significant damage to vision ( 1 ). Glucocorticoids, immune-suppressants, or biological agents, which are used for uveitis, are still faced with huge challenges, including restricted efficiency and long-term adverse events ( 2 , 3 ). Therefore, it is necessary to search for new medications that could treat this refractory sight-threatening disease.…”

Section: Introductionmentioning

confidence: 99%

Apremilast Regulates the Teff/Treg Balance to Ameliorate Uveitis via PI3K/AKT/FoxO1 Signaling Pathway

Chen

¹

,

Li

²

,

Li

³

et al. 2020

View full text Add to dashboard Cite

Autoimmune uveitis (AU), being one of the sight-threatening ocular inflammatory disorders, has been widely regarded by ophthalmologists and immunologists as a great challenge. Apremilast, a phosphodiesterase-4 inhibitor (PDE4i), which was approved by the U.S. Food and Drug Administration (FDA) for the treatment of active psoriatic arthritis in 2014, has been attracting researchers, who are exploring its efficiency and mechanism on uveitis. In this study, we used an experimental autoimmune uveitis (EAU), a representative model for human AU, to investigate the effect of apremilast on regulating anti-inflammatory mediators. Our study demonstrated that apremilast treatment resulted in a decrease in vascular leakage, macular edema, and inflammatory cell infiltration in the retina, corresponding to decreased clinical and pathological scores. Specifically, apremilast decreased the proportion and population of Th17 cells and increased the proportion and population of T regulatory (Treg) cells. Mechanistically, apremilast may regulate Th17 and Treg cells by inhibiting the phosphorylation of the phosphoinositide 3-kinase (PI3K)/protein kinase B(AKT)/Forkhead box O1 (FoxO1) signaling pathway. These findings suggested that apremilast alleviated EAU by regulating Th17 and Treg through the PI3K/AKT/FoxO1 pathway.

show abstract

“…A second phenomenon linked to IP has also been described namely anterior chamber-associated immune deviation (ACAID) ( 27 – 29 ) as has a similar phenomenon in the brain (brain-associated immune deviation, BRAID) ( 30 ). Immune deviation is a recognized immunological phenomenon in which antigen-specific immunity, usually in the form of cell-mediated delayed-type hypersensitivity (DTH), is suppressed while being “deviated” toward humoral immunity, usually the generation of IgG2 antibodies.…”

Section: Immune Privilege: How the Concept Arose And How It Has Blurrmentioning

confidence: 99%

Immune Privilege: The Microbiome and Uveitis

Mölzer

¹

,

Heissigerová

²

,

Wilson

³

et al. 2021

View full text Add to dashboard Cite

Immune privilege (IP), a term introduced to explain the unpredicted acceptance of allogeneic grafts by the eye and the brain, is considered a unique property of these tissues. However, immune responses are modified by the tissue in which they occur, most of which possess IP to some degree. The eye therefore displays a spectrum of IP because it comprises several tissues. IP as originally conceived can only apply to the retina as it contains few tissue-resident bone-marrow derived myeloid cells and is immunologically shielded by a sophisticated barrier – an inner vascular and an outer epithelial barrier at the retinal pigment epithelium. The vascular barrier comprises the vascular endothelium and the glia limitans. Immune cells do not cross the blood-retinal barrier (BRB) despite two-way transport of interstitial fluid, governed by tissue oncotic pressure. The BRB, and the blood-brain barrier (BBB) mature in the neonatal period under signals from the expanding microbiome and by 18 months are fully established. However, the adult eye is susceptible to intraocular inflammation (uveitis; frequency ~200/100,000 population). Uveitis involving the retinal parenchyma (posterior uveitis, PU) breaches IP, while IP is essentially irrelevant in inflammation involving the ocular chambers, uveal tract and ocular coats (anterior/intermediate uveitis/sclerouveitis, AU). Infections cause ~50% cases of AU and PU but infection may also underlie the pathogenesis of immune-mediated “non-infectious” uveitis. Dysbiosis accompanies the commonest form, HLA-B27–associated AU, while latent infections underlie BRB breakdown in PU. This review considers the pathogenesis of uveitis in the context of IP, infection, environment, and the microbiome.

show abstract

“…An alternative mechanism for the immunosuppressive effect of Mtx and other immunosuppressants has been proposed: in humans, hypomethylation of the TSDR ( T reg -specific demethylated region) is required for the functional stability of peripherally expanding FoxP3 + p T reg [ 171 ] and correlates with the duration of oral immunosuppressive therapy. This indicates that in patients, conventional immunosuppression can induce p T reg leading to remission of the disease (reviewed in [ 172 ]). This finding is particularly interesting with regard to folate being a mediator of epigenetic programming ( Figure 3 ) and emphasizes the importance of coordinating appropriate treatment regimens with the dynamics and kinetics of disease progression.…”

Section: Folate Deficiency and Current Therapy For Admentioning

confidence: 99%

A Role for Folate in Microbiome-Linked Control of Autoimmunity

Mölzer

¹

,

Kuffová

²

,

Forrester

³

2021

Journal of Immunology Research

View full text Add to dashboard Cite

The microbiome exerts considerable control over immune homeostasis and influences susceptibility to autoimmune and autoinflammatory disease (AD/AID) such as inflammatory bowel disease (IBD), multiple sclerosis (MS), type 1 diabetes (T1D), psoriasis, and uveitis. In part, this is due to direct effects of the microbiome on gastrointestinal (GI) physiology and nutrient transport, but also to indirect effects on immunoregulatory controls, including induction and stabilization of T regulatory cells ( T reg ). Secreted bacterial metabolites such as short-chain fatty acids (SCFA) are under intense investigation as mediators of these effects. In contrast, folate (vitamin B9), an essential micronutrient, has attracted less attention, possibly because it exerts global physiological effects which are difficult to differentiate from specific effects on the immune system. Here, we review the role of folate in AD/AID with some emphasis on sight-threatening autoimmune uveitis. Since folate is required for the generation and maintenance of T reg , we propose that one mechanism for microbiome-based control of AD/AID is via folate-dependent induction of GI tract T reg , particularly colonic T reg , via anergic T cells ( T an ). Hence, folate supplementation has potential prophylactic and/or therapeutic benefit in AID/AD.

show abstract

Resolution of uveitis

Cited by 31 publications

References 94 publications

Apremilast Regulates the Teff/Treg Balance to Ameliorate Uveitis via PI3K/AKT/FoxO1 Signaling Pathway

Apremilast Regulates the Teff/Treg Balance to Ameliorate Uveitis via PI3K/AKT/FoxO1 Signaling Pathway

Immune Privilege: The Microbiome and Uveitis

A Role for Folate in Microbiome-Linked Control of Autoimmunity

Contact Info

Product

Resources

About