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KS23, a novel peptide derived from adiponectin, inhibits retinal inflammation and downregulates the proportions of Th1 and Th17 cells during experimental autoimmune uveitis.

ABSTRACT: BACKGROUND:Uveitis is a potentially sight-threatening form of ocular inflammation that affects the uvea in the wall of the eye. Currently available treatments for uveitis have exhibited profound adverse side effects. However, KS23 is a novel 23-amino-acid anti-inflammatory peptide derived from adiponectin that may have the capability to function as a safe alternative to these existing treatment options. We, therefore, evaluated the preventive effect of KS23 in experimental autoimmune uveitis (EAU). METHODS:EAU was induced in mice via immunization with the peptide interphotoreceptor retinoid binding protein 161-180 (IRBP161-180). KS23 was then administered every 2?days via intraperitoneal injection to induce protection against EAU. Clinical and histopathological scores were employed to evaluate the disease progression. Inflammatory cytokines were also quantified using ELISA, and the expression levels of specific chemokines and chemokine receptors were assessed via qRT-PCR. In addition, the proportions of Th1 and Th17 cells were detected via flow cytometry, and the expression levels of specific proteins were quantified from the retina of mice using western blot analysis, to elucidate the specific mechanism of action employed by KS23 to suppress the inflammation associated with EAU. RESULTS:KS23 was found to significantly improve EAU-associated histopathological scores, while decreasing the expression of pro-inflammatory cytokines (IFN-?, TNF-?, IL-6, and IL-17A), chemokines (LARC, RANTES, MIG, IP-10), and chemokine receptors (CCR6 and CXCR3). The proportions of Th1 and Th17 cells were also suppressed following intraperitoneal injection with KS23. The anti-inflammatory mechanism employed by KS23 was determined to be associated with the activation of AMPK and subsequent inhibition of NF-?B. CONCLUSIONS:KS23 decreased the proportions of Th1 and Th17 cells to effectively ameliorate the progression of EAU. It may, therefore, serve as a promising potential therapeutic agent for uveitis.

SUBMITTER: Niu T

PROVIDER: S-EPMC6935244 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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KS23, a novel peptide derived from adiponectin, inhibits retinal inflammation and downregulates the proportions of Th1 and Th17 cells during experimental autoimmune uveitis.

Niu Tian T Cheng Lu L Wang Hanying H Zhu Shaopin S Yang Xiaolu X Liu Kun K Jin Huiyi H Xu Xun X

Journal of neuroinflammation 20191228 1

<h4>Background</h4>Uveitis is a potentially sight-threatening form of ocular inflammation that affects the uvea in the wall of the eye. Currently available treatments for uveitis have exhibited profound adverse side effects. However, KS23 is a novel 23-amino-acid anti-inflammatory peptide derived from adiponectin that may have the capability to function as a safe alternative to these existing treatment options. We, therefore, evaluated the preventive effect of KS23 in experimental autoimmune uve ...[more]

PMID: 31883532

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Project description:BackgroundThere is consensus that experimental autoimmune encephalomyelitis (EAE) can be mediated by myelin specific T cells of Th1 as well as of Th17 phenotype, but the contribution of either subset to the pathogenic process has remained controversial. In this report, we compare functional differences and pathogenic potential of "monoclonal" T cell lines that recognize myelin oligodendrocyte glycoprotein (MOG) with the same transgenic TCR but are distinguished by an IFN-? producing Th1-like and IL-17 producing Th17-like cytokine signature.Methods and findingsCD4+ T cell lines were derived from the transgenic mouse strain 2D2, which expresses a TCR recognizing MOG peptide 35-55 in the context of I-A(b). Adoptive transfer of Th1 cells into lymphopenic (Rag2?/?) recipients, predominantly induced "classic" paralytic EAE, whereas Th17 cells mediated "atypical" ataxic EAE in approximately 50% of the recipient animals. Combination of Th1 and Th17 cells potentiated the encephalitogenicity inducing classical EAE exclusively. Th1 and Th17 mediated EAE lesions differed in their composition but not in their localization within the CNS. While Th1 lesions contained IFN-?, but no IL-17 producing T cells, the T cells in Th17 lesions showed plasticity, substantially converting to IFN-? producing Th1-like cells. Th1 and Th17 cells differed drastically by their lytic potential. Th1 but not Th17 cells lysed autoantigen presenting astrocytes and fibroblasts in vitro in a contact-dependent manner. In contrast, Th17 cells acquired cytotoxic potential only after antigenic stimulation and conversion to IFN-? producing Th1 phenotype.ConclusionsOur data demonstrate that both Th1 and Th17 lineages possess the ability to induce CNS autoimmunity but can function with complementary as well as differential pathogenic mechanisms. We propose that Th17-like cells producing IL-17 are required for the generation of atypical EAE whereas IFN-? producing Th1 cells induce classical EAE.

Dataset Information

KS23, a novel peptide derived from adiponectin, inhibits retinal inflammation and downregulates the proportions of Th1 and Th17 cells during experimental autoimmune uveitis.

Publications

KS23, a novel peptide derived from adiponectin, inhibits retinal inflammation and downregulates the proportions of Th1 and Th17 cells during experimental autoimmune uveitis.

Similar Datasets

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