In Utero Arsenic Exposure Is Associated With Impaired Thymic Function in Newborns Possibly Via Oxidative Stress and Apoptosis

Ahmed, Sultan; Ahsan, Khalid; Kippler, Maria; Mily, Akhirunnesa; Wagatsuma, Yukiko; Hoque, A. M. Waheedul; Ngom, Pa Tamba; Arifeen, Shams El; Raqib, Rubhana; Vahter, Marie

doi:10.1093/toxsci/kfs202

Cited by 113 publications

(71 citation statements)

References 36 publications

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“…2). There are also reports showing that prenatal arsenic exposures are related to the altered lymphoid cell development and thymic atrophy (Ahmed et al, 2012; Raqib et al, 2009). It is very possible that these early life developmental suppressions are associated with the high sensitivity of the DN T cell population.…”

Section: Discussionmentioning

confidence: 99%

Environmentally relevant concentrations of arsenite and monomethylarsonous acid inhibit IL-7/STAT5 cytokine signaling pathways in mouse CD3+CD4-CD8- double negative thymus cells

Lauer

Liu

et al. 2016

Toxicology Letters

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Environmental arsenic exposure is a public health issue. Immunotoxicity induced by arsenic has been reported in humans and animal models. The purpose of this study was to evaluate mechanisms of As+3 and MMA+3 toxicity in mouse thymus cells. Because we know that MMA+3 inhibits IL-7 signaling in mouse bone marrow pre-B cells, we studied the influence of As+3 and MMA+3 on T cell development in the thymus at the earliest stage of T cell development (CD4− CD8−, double negative, DN) which requires IL-7 dependent signaling. We found in a DN thymus cell line (D1) that a low concentration of MMA+3 (50 nM) suppressed IL-7 dependent JAK1, 3 and STAT5 signaling. As+3 suppressed STAT5 and Jak3 activations at higher concentrations (500 nM). Cell surface expression of the IL-7 receptor (CD127) was also suppressed by 50 nM MMA+3, but was increased by 500 nM As+3, indicating possible differences in the mechanisms of action of these agents. A decrease in cyclin D1 protein expression was observed in D1 cells exposed to As+3 at 500 nM and MMA+3 starting at 50 nM, suggesting that arsenic at these environmentally-relevant doses suppresses early T cell development through the inhibition of IL-7 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Environmentally relevant concentrations of arsenite and monomethylarsonous acid inhibit IL-7/STAT5 cytokine signaling pathways in mouse CD3+CD4-CD8- double negative thymus cells

Lauer

Liu

et al. 2016

Toxicology Letters

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“…Neonatal immunotoxicity can occur well below adult safety thresholds (30). Arsenic exposure may lead to direct effects on immunity through epigenetic programing involving leukocytes and metabolic physiology (31–36). …”

Section: Developmental Immunotoxicologymentioning

confidence: 99%

The Role of Environmental Factors in Modulating Immune Responses in Early Life

2014

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The concept of immunological memory stipulates that past exposures shape present immune function. These exposures include not only specific antigens impacting adaptive immune memory but also conserved pathogen or danger associated molecular patterns that mold innate immune responses for prolonged periods of time. It should thus not come as a surprise that there is a vast range of external or environmental factors that impact immunity. The importance of environmental factors modulating immunity is most readily recognized in early life, a period of rapidly changing environments. We here summarize available data on the role of environment shaping immune development and from it derive an overarching hypothesis relating the underlying molecular mechanisms and evolutionary principles involved.

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“…A study conducted in a Bangladeshi cohort reported that prenatal arsenic exposure was associated with infant morbidity and led to reduction in thymic index, compromised thymic function, also indicating subsequent immune-suppression in childhood (Ahmed et al, 2012).…”

Section: All Of the Above Observations Indicate An Important Immunomomentioning

confidence: 99%

Arsenic-induced dose-dependent modulation of the NF-κB/IL-6 axis in thymocytes triggers differential immune responses

et al. 2016

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In Utero Arsenic Exposure Is Associated With Impaired Thymic Function in Newborns Possibly Via Oxidative Stress and Apoptosis

Cited by 113 publications

References 36 publications

Environmentally relevant concentrations of arsenite and monomethylarsonous acid inhibit IL-7/STAT5 cytokine signaling pathways in mouse CD3+CD4-CD8- double negative thymus cells

Environmentally relevant concentrations of arsenite and monomethylarsonous acid inhibit IL-7/STAT5 cytokine signaling pathways in mouse CD3+CD4-CD8- double negative thymus cells

The Role of Environmental Factors in Modulating Immune Responses in Early Life

Arsenic-induced dose-dependent modulation of the NF-κB/IL-6 axis in thymocytes triggers differential immune responses

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