A peptide mimic of SOCS1 modulates equine peripheral immune cells in vitro and ocular effector functions in vivo: implications for recurrent uveitis DOI Creative Commons
Lauren Stewart Stafford, Caryn E. Plummer, W. Clay Smith

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 10, 2025

Recurrent uveitis (RU), an autoimmune disease, is a leading cause of ocular detriment in humans and horses. Equine human RU share many similarities including spontaneous disease aberrant cytokine signaling. Reduced levels SOCS1, critical regulator signaling, associated with several diseases. Topical administration SOCS1-KIR, peptide mimic was previously correlated to reduced pathologies within ERU patients. To further assess the translational potential SOCS1 mimetic treat RU, we assessed peptide-mediated modulation immune functions vitro, using equine peripheral blood mononuclear cells (PBMC), vivo through topical SOCS1-KIR into eyes experimental (non-uveitic) PBMCs from non-uveitic control horses were cultured or without pretreatment, followed by 72 hours mitogen stimulation. Proliferation MTT, production cell supernatants Luminex. carrier eye-drops topically applied horse twice daily for 21 days, enucleation isolation aqueous vitreous humor. Histology used treatment safety localization treated eyes. Cytokine secretion humor vitreous, isolated eyes, measured Following proliferation significantly decreased control, but not ERU-derived PBMCs. Despite differential regulation cellular proliferation, TNFα IL-10 PHA-stimulated PBMC. increased PBMC IL-8. Topically administered well tolerated. Although undetectable eye, had significant reductions IL-10. Interestingly, found that while healthy PBMC, differentially modulated IP-10 production, RANTES these two groups suggesting possible differences types activation status. safe eye reduces cytokines serving as biomarkers drug efficacy future clinical trial.

Language: Английский

A peptide mimic of SOCS1 modulates equine peripheral immune cells in vitro and ocular effector functions in vivo: implications for recurrent uveitis DOI Creative Commons
Lauren Stewart Stafford, Caryn E. Plummer, W. Clay Smith

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 10, 2025

Recurrent uveitis (RU), an autoimmune disease, is a leading cause of ocular detriment in humans and horses. Equine human RU share many similarities including spontaneous disease aberrant cytokine signaling. Reduced levels SOCS1, critical regulator signaling, associated with several diseases. Topical administration SOCS1-KIR, peptide mimic was previously correlated to reduced pathologies within ERU patients. To further assess the translational potential SOCS1 mimetic treat RU, we assessed peptide-mediated modulation immune functions vitro, using equine peripheral blood mononuclear cells (PBMC), vivo through topical SOCS1-KIR into eyes experimental (non-uveitic) PBMCs from non-uveitic control horses were cultured or without pretreatment, followed by 72 hours mitogen stimulation. Proliferation MTT, production cell supernatants Luminex. carrier eye-drops topically applied horse twice daily for 21 days, enucleation isolation aqueous vitreous humor. Histology used treatment safety localization treated eyes. Cytokine secretion humor vitreous, isolated eyes, measured Following proliferation significantly decreased control, but not ERU-derived PBMCs. Despite differential regulation cellular proliferation, TNFα IL-10 PHA-stimulated PBMC. increased PBMC IL-8. Topically administered well tolerated. Although undetectable eye, had significant reductions IL-10. Interestingly, found that while healthy PBMC, differentially modulated IP-10 production, RANTES these two groups suggesting possible differences types activation status. safe eye reduces cytokines serving as biomarkers drug efficacy future clinical trial.

Language: Английский

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