Arsenic exposure impels CD4 commitment in thymus and suppress T cell cytokine secretion by increasing regulatory T cells

Abstract Arsenic is globally infamous for inducing immunosuppression associated with prevalence of opportunistic infection in exposed population, although the mechanism remains elusive. In this study, we investigate the effect of arsenic exposure on thymocyte lineage commitment and the involvement o...

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Autores principales: Ruchi Gera, Vikas Singh, Sumonto Mitra, Anuj Kumar Sharma, Alok Singh, Arunava Dasgupta, Dhirendra Singh, Mahadeo Kumar, Pankaj Jagdale, Satyakam Patnaik, Debabrata Ghosh
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/99de3ee5bebe45608b0bf0c74f753999
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spelling oai:doaj.org-article:99de3ee5bebe45608b0bf0c74f7539992021-12-02T16:06:54ZArsenic exposure impels CD4 commitment in thymus and suppress T cell cytokine secretion by increasing regulatory T cells10.1038/s41598-017-07271-z2045-2322https://doaj.org/article/99de3ee5bebe45608b0bf0c74f7539992017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07271-zhttps://doaj.org/toc/2045-2322Abstract Arsenic is globally infamous for inducing immunosuppression associated with prevalence of opportunistic infection in exposed population, although the mechanism remains elusive. In this study, we investigate the effect of arsenic exposure on thymocyte lineage commitment and the involvement of regulatory T cells (Treg) in arsenic-induced immunosuppression. Male Balb/c mice were exposed to 0.038, 0.38 and 3.8 ppm sodium arsenite for 7, 15 and 30 days through oral gavage. Arsenic exposure promoted CD4 lineage commitment in a dose dependent manner supported by the expression of ThPOK in thymus. Arsenic also increased splenic CD4+ T cells and promoted their differentiation into Treg cells. In parallel, arsenic exposure induced immunosuppression characterized by low cytokine secretion from splenocytes and increased susceptibility to Mycobacterium fortuitum (M. fortuitum) infection. Therefore, we linked arsenic-induced rise in Treg cells with suppressed Th1 and Th2 related cytokines, which has been reversed by inhibition of Treg cells in-vivo using wortmannin. Other parameters like body weight, kidney and liver function, histoanatomy of thymus and spleen as well as thymocyte and splenocytes viability were unaltered by arsenic exposure. Taken together our findings indicated that environmentally relevant dose of arsenic enhanced differentiation of Treg cells which in turn induce immunosuppression in experimental animals.Ruchi GeraVikas SinghSumonto MitraAnuj Kumar SharmaAlok SinghArunava DasguptaDhirendra SinghMahadeo KumarPankaj JagdaleSatyakam PatnaikDebabrata GhoshNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Ruchi Gera
Vikas Singh
Sumonto Mitra
Anuj Kumar Sharma
Alok Singh
Arunava Dasgupta
Dhirendra Singh
Mahadeo Kumar
Pankaj Jagdale
Satyakam Patnaik
Debabrata Ghosh
Arsenic exposure impels CD4 commitment in thymus and suppress T cell cytokine secretion by increasing regulatory T cells
description Abstract Arsenic is globally infamous for inducing immunosuppression associated with prevalence of opportunistic infection in exposed population, although the mechanism remains elusive. In this study, we investigate the effect of arsenic exposure on thymocyte lineage commitment and the involvement of regulatory T cells (Treg) in arsenic-induced immunosuppression. Male Balb/c mice were exposed to 0.038, 0.38 and 3.8 ppm sodium arsenite for 7, 15 and 30 days through oral gavage. Arsenic exposure promoted CD4 lineage commitment in a dose dependent manner supported by the expression of ThPOK in thymus. Arsenic also increased splenic CD4+ T cells and promoted their differentiation into Treg cells. In parallel, arsenic exposure induced immunosuppression characterized by low cytokine secretion from splenocytes and increased susceptibility to Mycobacterium fortuitum (M. fortuitum) infection. Therefore, we linked arsenic-induced rise in Treg cells with suppressed Th1 and Th2 related cytokines, which has been reversed by inhibition of Treg cells in-vivo using wortmannin. Other parameters like body weight, kidney and liver function, histoanatomy of thymus and spleen as well as thymocyte and splenocytes viability were unaltered by arsenic exposure. Taken together our findings indicated that environmentally relevant dose of arsenic enhanced differentiation of Treg cells which in turn induce immunosuppression in experimental animals.
format article
author Ruchi Gera
Vikas Singh
Sumonto Mitra
Anuj Kumar Sharma
Alok Singh
Arunava Dasgupta
Dhirendra Singh
Mahadeo Kumar
Pankaj Jagdale
Satyakam Patnaik
Debabrata Ghosh
author_facet Ruchi Gera
Vikas Singh
Sumonto Mitra
Anuj Kumar Sharma
Alok Singh
Arunava Dasgupta
Dhirendra Singh
Mahadeo Kumar
Pankaj Jagdale
Satyakam Patnaik
Debabrata Ghosh
author_sort Ruchi Gera
title Arsenic exposure impels CD4 commitment in thymus and suppress T cell cytokine secretion by increasing regulatory T cells
title_short Arsenic exposure impels CD4 commitment in thymus and suppress T cell cytokine secretion by increasing regulatory T cells
title_full Arsenic exposure impels CD4 commitment in thymus and suppress T cell cytokine secretion by increasing regulatory T cells
title_fullStr Arsenic exposure impels CD4 commitment in thymus and suppress T cell cytokine secretion by increasing regulatory T cells
title_full_unstemmed Arsenic exposure impels CD4 commitment in thymus and suppress T cell cytokine secretion by increasing regulatory T cells
title_sort arsenic exposure impels cd4 commitment in thymus and suppress t cell cytokine secretion by increasing regulatory t cells
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/99de3ee5bebe45608b0bf0c74f753999
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