Oral tolerance in a murine model of relapsing experimental autoimmune uveoretinitis (EAU): induction of protective tolerance in primed animals

Thurau, Stephan; Chan, Chi‐Chao; Nussenblatt, Robert B.; Caspi, Rachel R

doi:10.1046/j.1365-2249.1997.4571356.x

Cited by 138 publications

(109 citation statements)

References 31 publications

Supporting

Mentioning

104

Contrasting

Unclassified

Order By: Relevance

“…The severity of EAU was graded 0-4 as described previously (Thurau et al 1997). Briefly, the clinical scoring was based on vessel dilatation, the number of vessel white focal lesions, vessel white linear lesions and hemorrhages, and the extent of retinal detachment.…”

Section: Evaluation Of Eaumentioning

confidence: 99%

Prevention of experimental autoimmune uveoretinitis by blockade of osteopontin with small interfering RNA

Iwata

Kitamura

Saito

et al. 2010

Experimental Eye Research

View full text Add to dashboard Cite

Osteopontin (OPN) is elevated during the progression of experimental autoimmune uveoretinitis (EAU) in C57BL/6 (B6) mice. Furthermore, EAU symptoms are ameliorated in OPN knockout mice or in B6 mice treated with anti-OPN antibody (M5). Recently, OPN has been shown to promote the Th1 response not only in the extracellular space as a secretory protein but also in cytosol as a signaling component. Thus, we attempted to reduce OPN in both compartments by using a small interfering RNA (siRNA) targeting the OPN coding sequence (OPN-siRNA).

show abstract

Section: Evaluation Of Eaumentioning

confidence: 99%

Prevention of experimental autoimmune uveoretinitis by blockade of osteopontin with small interfering RNA

Iwata

Kitamura

Saito

et al. 2010

Experimental Eye Research

View full text Add to dashboard Cite

show abstract

“…The severity of EAU was graded 0 -4, as described previously (24). Briefly, the clinical scoring was based on vessel dilatation, the number of vessel white focal lesions, vessel white linear lesions, hemorrhages, and the extent of retinal detachment.…”

Section: Evaluation Of Eaumentioning

confidence: 99%

Osteopontin Aggravates Experimental Autoimmune Uveoretinitis in Mice

Kitamura

Iwabuchi

Kawa

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

Human endogenous uveitis is a common sight-threatening intraocular inflammatory disease and has been studied extensively using a murine model of experimental autoimmune uveoretinitis (EAU). It is possibly mediated by Th1 immune responses. In the present study, we investigated the role of osteopontin (OPN), a protein with pleiotropic functions that contributes to the development of Th1 cell-mediated immunity. Accompanying EAU progression, OPN was elevated in wild-type (WT) mice that had been immunized with human interphotoreceptor retinoid-binding protein (hIRBP) peptide 1–20. OPN-deficient (OPN−/−) mice showed milder EAU progression in clinical and histopathological scores compared with those of WT mice. The T cells from hIRBP-immunized OPN−/− mice exhibited reduced Ag-specific proliferation and proinflammatory cytokine (TNF-α and IFN-γ) production compared with those of WT T cells. When hIRBP-immunized WT mice were administered M5 Ab reacting to SLAYGLR sequence, a cryptic binding site to integrins within OPN, EAU development was significantly ameliorated. T cells from hIRBP-immunized WT mice showed significantly reduced proliferative responses and proinflammatory cytokine production upon stimulation with hIRBP peptide in the presence of M5 Ab in the culture. Our present results demonstrate that OPN may represent a novel therapeutic target to control uveoretinitis.

show abstract

“…The presence of vessel dilatation, vessel white focal lesions, vessel white linear lesions, retinal hemorrhaging, and retinal detachment was determined. According to the severity of these findings, the EAU clinical scores were graded 0-4 as described by Thurau et al [41]. When the two ophthalmologists had different scores, the mean value of each score was calculated and then it was shown as the clinical grade at that point.…”

Section: Induction Of Eau Mab Treatment and Assessmentmentioning

confidence: 99%

The role of the ICOS/B7RP‐1 T cell costimulatory pathway in murine experimental autoimmune uveoretinitis

et al. 2006

View full text Add to dashboard Cite

ICOS/B7RP-1 is a new member of the CD28/B7 family of costimulatory molecules and plays differential roles in autoimmune diseases. In this study, we examined the role of ICOS/B7RP-1 pathway in the pathogenesis of mouse experimental autoimmune uveoretinitis (EAU), an animal model of human autoimmune uveitis. ICOS expression was found on infiltrating CD4 + T cells in the region of the retina in EAU-induced mice. The anti-B7RP-1 monoclonal antibody (mAb)-treated or ICOS-deficient mice showed a substantial reduction of disease scores. Blockade of ICOS/B7RP-1 interaction during the effector phase ameliorated the disease, whereas its blockade during the induction phase exhibited no significant effect. Moreover, administration of anti-B7RP-1 mAb effectively ameliorated the disease induced by adoptive transfer of pathogenic T cells. The anti-B7RP-1 mAb treatment inhibited the expansion and/or effector function of pathogenic T cells, given that proliferative response and IFN-c production by lymph node cells were reduced upon restimulation with the antigen peptide in vitro. These results suggest that the ICOS/B7RP-1 interaction plays a critical role in the pathogenesis of uveitis. We also indicated that ICOS-mediated costimulation plays differential roles in EAU and experimental autoimmune encephalomyelitis, which is also a Th1 disease induced in the same manner as EAU.

show abstract

Oral tolerance in a murine model of relapsing experimental autoimmune uveoretinitis (EAU): induction of protective tolerance in primed animals

Cited by 138 publications

References 31 publications

Prevention of experimental autoimmune uveoretinitis by blockade of osteopontin with small interfering RNA

Prevention of experimental autoimmune uveoretinitis by blockade of osteopontin with small interfering RNA

Osteopontin Aggravates Experimental Autoimmune Uveoretinitis in Mice

The role of the ICOS/B7RP‐1 T cell costimulatory pathway in murine experimental autoimmune uveoretinitis

Contact Info

Product

Resources

About