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Superoxide Dismutase 3 Controls the Activation and Differentiation of CD4(+)T Cells

Superoxide dismutase 3 (SOD3), a well-known antioxidant has been shown to possess immunomodulatory properties through inhibition of T cell differentiation. However, the underlying inhibitory mechanism of SOD3 on T cell differentiation is not well understood. In this study, we investigated the effect...

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Autores principales: Agrahari, Gaurav, Sah, Shyam Kishor, Bang, Chul Hwan, Kim, Yeong Ho, Kim, Tae-Yoon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947887/
https://www.ncbi.nlm.nih.gov/pubmed/33717151
http://dx.doi.org/10.3389/fimmu.2021.628117
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author Agrahari, Gaurav
Sah, Shyam Kishor
Bang, Chul Hwan
Kim, Yeong Ho
Kim, Tae-Yoon
author_facet Agrahari, Gaurav
Sah, Shyam Kishor
Bang, Chul Hwan
Kim, Yeong Ho
Kim, Tae-Yoon
author_sort Agrahari, Gaurav
collection PubMed
description Superoxide dismutase 3 (SOD3), a well-known antioxidant has been shown to possess immunomodulatory properties through inhibition of T cell differentiation. However, the underlying inhibitory mechanism of SOD3 on T cell differentiation is not well understood. In this study, we investigated the effect of SOD3 on anti-CD3/CD28- or phorbol myristate acetate (PMA) and ionomycin (ION)-mediated activation of mouse naive CD4(+) T cells. Our data showed that SOD3 suppressed the expression of activation-induced surface receptor proteins such as CD25, and CD69, and cytokines production. Similarly, SOD3 was found to reduce CD4(+)T cells proliferation and suppress the activation of downstream pathways such as ERK, p38, and NF-κB. Moreover, naïve CD4(+)T cells isolated from global SOD3 knock-out mice showed higher expression of CD25, CD69, and CD71, IL-2 production, proliferation, and downstream signals compared to wild-type CD4(+)T cells. Whereas, the use of DETCA, a known inhibitor of SOD3 activity, found to nullify the inhibitory effect of SOD3 on CD4(+)T cell activation of both SOD3 KO and wild-type mice. Furthermore, the expression of surface receptor proteins, IL-2 production, and downstream signals were also reduced in Th2 and Th17 differentiated cells upon SOD3 treatment. Overall, our data showed that SOD3 can attenuate CD4(+)T cell activation through modulation of the downstream signalings and restrict CD4(+)T cell differentiation. Therefore, SOD3 can be a promising therapeutic for T cell-mediated disorders.
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spelling pubmed-79478872021-03-12 Superoxide Dismutase 3 Controls the Activation and Differentiation of CD4(+)T Cells Agrahari, Gaurav Sah, Shyam Kishor Bang, Chul Hwan Kim, Yeong Ho Kim, Tae-Yoon Front Immunol Immunology Superoxide dismutase 3 (SOD3), a well-known antioxidant has been shown to possess immunomodulatory properties through inhibition of T cell differentiation. However, the underlying inhibitory mechanism of SOD3 on T cell differentiation is not well understood. In this study, we investigated the effect of SOD3 on anti-CD3/CD28- or phorbol myristate acetate (PMA) and ionomycin (ION)-mediated activation of mouse naive CD4(+) T cells. Our data showed that SOD3 suppressed the expression of activation-induced surface receptor proteins such as CD25, and CD69, and cytokines production. Similarly, SOD3 was found to reduce CD4(+)T cells proliferation and suppress the activation of downstream pathways such as ERK, p38, and NF-κB. Moreover, naïve CD4(+)T cells isolated from global SOD3 knock-out mice showed higher expression of CD25, CD69, and CD71, IL-2 production, proliferation, and downstream signals compared to wild-type CD4(+)T cells. Whereas, the use of DETCA, a known inhibitor of SOD3 activity, found to nullify the inhibitory effect of SOD3 on CD4(+)T cell activation of both SOD3 KO and wild-type mice. Furthermore, the expression of surface receptor proteins, IL-2 production, and downstream signals were also reduced in Th2 and Th17 differentiated cells upon SOD3 treatment. Overall, our data showed that SOD3 can attenuate CD4(+)T cell activation through modulation of the downstream signalings and restrict CD4(+)T cell differentiation. Therefore, SOD3 can be a promising therapeutic for T cell-mediated disorders. Frontiers Media S.A. 2021-02-25 /pmc/articles/PMC7947887/ /pubmed/33717151 http://dx.doi.org/10.3389/fimmu.2021.628117 Text en Copyright © 2021 Agrahari, Sah, Bang, Kim and Kim http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Agrahari, Gaurav
Sah, Shyam Kishor
Bang, Chul Hwan
Kim, Yeong Ho
Kim, Tae-Yoon
Superoxide Dismutase 3 Controls the Activation and Differentiation of CD4(+)T Cells
title Superoxide Dismutase 3 Controls the Activation and Differentiation of CD4(+)T Cells
title_full Superoxide Dismutase 3 Controls the Activation and Differentiation of CD4(+)T Cells
title_fullStr Superoxide Dismutase 3 Controls the Activation and Differentiation of CD4(+)T Cells
title_full_unstemmed Superoxide Dismutase 3 Controls the Activation and Differentiation of CD4(+)T Cells
title_short Superoxide Dismutase 3 Controls the Activation and Differentiation of CD4(+)T Cells
title_sort superoxide dismutase 3 controls the activation and differentiation of cd4(+)t cells
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947887/
https://www.ncbi.nlm.nih.gov/pubmed/33717151
http://dx.doi.org/10.3389/fimmu.2021.628117
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