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

Gera, Ruchi; Singh, Vikas; Mitra, Sumonto; Sharma, A.; Singh, Alok R.; Dasgupta, Arunava; Singh, Dhirendra Kumar; Kumar, Mukesh; Jagdale, Pankaj; Patnaik, Satyakam; Ghosh, Debabrata

doi:10.1038/s41598-017-07271-z

Cited by 42 publications

(17 citation statements)

References 61 publications

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“…Particularly, male BALB/c mice exposed to 0.038, 0.38 and 3.8 ppm sodium arsenite for 7, 15 and 30 days through oral gavage showed a significant dose-dependent increase in the ThPOK expression levels in thymus, suggesting an impairment in the regulation of CD4+ T cells differentiation. In the spleen, As increased the number of CD4+ T cells and promoted their differentiation into Treg cells, however, a low secretion of IFN-γ, TNF-α, IL-12, IL-4, IL-5 and IL-10 cytokines was observed in splenocytes ( Gera et al 2017 ). Activation of NF-kB and downstream signaling was shown to induce As-associated immune suppression ( Choudhury et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Toxic metal exposure as a possible risk factor for COVID-19 and other respiratory infectious diseases

Skalny

Lima

Tao

et al. 2020

Food and Chemical Toxicology

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Multiple medical, lifestyle, and environmental conditions, including smoking and particulate pollution, have been considered as risk factors for CO rona VI rus D isease 2019 (COVID-19) susceptibility and severity. Taking into account the high level of toxic metals in both particulate matter (PM2.5) and tobacco smoke, the objective of this review is to discuss recent data on the role of heavy metal exposure in development of respiratory dysfunction, immunotoxicity, and severity of viral diseases in epidemiological and experimental studies, as to demonstrate the potential crossroads between heavy metal exposure and COVID-19 severity risk. The existing data demonstrate that As, Cd, Hg, and Pb exposure is associated with respiratory dysfunction and respiratory diseases (COPD, bronchitis). These observations corroborate laboratory findings on the role of heavy metal exposure in impaired mucociliary clearance, reduced barrier function, airway inflammation, oxidative stress, and apoptosis. The association between heavy metal exposure and severity of viral diseases, including influenza and respiratory syncytial virus has been also demonstrated. The latter may be considered a consequence of adverse effects of metal exposure on adaptive immunity. Therefore, reduction of toxic metal exposure may be considered as a potential tool for reducing susceptibility and severity of viral diseases affecting the respiratory system, including COVID-19.

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Section: Introductionmentioning

confidence: 99%

Toxic metal exposure as a possible risk factor for COVID-19 and other respiratory infectious diseases

Skalny

Lima

Tao

et al. 2020

Food and Chemical Toxicology

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“…The disruption of arsenic on the immune inflammatory homeostasis was inseparable from the involvement of cytokines controlled by various immune cells [ 18 – 20 ]. Our research found that the classic inflammatory factor, Tnf - α , did not change at 1 and 3 months but declined at 12 months under 25 mg/L NaAsO 2 treatment as well as decreased at 3 and 12 months in the case of 50 mg/L NaAsO 2 exposure in mice (Fig.…”

Section: Resultsmentioning

confidence: 99%

Chronic arsenic exposure induces the time-dependent modulation of inflammation and immunosuppression in spleen

Yan

Zhang

et al. 2020

Cell Biosci

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Background Arsenic exposure has become a matter of worldwide concern, which is associated with immune-related diseases. However, little is known about its effect on inflammatory immune-related homeostasis. The purpose of our study was to understand the potential tuning of above responses exerted by chronic arsenic exposure. Methods Kunming mice were treated with 25 and 50 mg/L sodium arsenite for 1, 3 and 12 months via drinking water. At different endpoints of arsenic exposure, all animals and the whole spleen of the mice were weighed. The total arsenic levels of spleen were determined by the HPLC-HG-AFS method. Splenic NF-κB, MAPK and NRF2 protein levels by treatment of 25 mg/L NaAsO 2 for 1, 3 and 12 months and 25 mg/L and 50 mg/L NaAsO 2 for 12 months were assessed by western blot. Total RNA of spleen was isolated and relative mRNA levels of Foxp3 , Il - 10 , Tnf - α , Il - 6 , Ifn - γ , Il - 1β and Il - 12 were measured by real-time PCR. Results Our results shown that NF-κB were continuously activated with treatment of 25 mg/L arsenic from 1, 3 to 12 months and 50 mg/L arsenic for 12 months. The transcription factor Foxp3 increased at 1 month but decreased at 3 and 12 months no matter 25 or 50 mg/L arsenic exposure. However, cytokine Il - 10 always showed increased trend in mice treated with 25 or 50 mg/L arsenic for 1, 3 and 12 months. The transcriptional profiles of Tnf - α , Il - 1β , Il - 6 , Ifn - γ and Il - 12 revealed transient elevation at 1 and 3 months but shown significant decrease at 12 months on the whole. In addition, the sustained activation of inflammatory MAPK and anti-oxidative Nrf2 signaling pathways were observed in mice exposed to arsenic for 1, 3 and 12 months. Conclusion In summary, our experiment in vivo suggested chronic arsenic exposure induces the time-dependent modulation of the inflammation and immunosuppression in spleen, which may be related to the activation of Tregs induced by MAPK/NF-κB as well as the increased transcription level of Foxp3 and Il - 10 .

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“…Cavassni et al 31 found significantly increased numbers of Treg cells after recovery from severe sepsis and this was related to increased tumour growth and the inhibition of the antitumor effects of CD8 + T cells. Exposure to environmental toxicants, such as arsenic, promotes the differentiation of Treg cells and thus prevents Th1- and Th2-related cytokine production and increases susceptibility to opportunistic infections, such as tuberculosis 32 , 33 . These findings suggest that increases in Treg cells inhibit effector T cell activity and contribute to the development of immunosuppressive microenvironments, thus resulting in adverse health effects, such as immune evasion and cancer progression 34 – 36 .…”

Section: Introductionmentioning

confidence: 99%

Formaldehyde exposure induces regulatory T cell-mediated immunosuppression via calcineurin-NFAT signalling pathway

Park

Yang

Song

et al. 2020

Sci Rep

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In this study, we investigated the effects of Formaldehyde (FA) exposure on splenic immune responses wherein helper T cells become activated and differentiate into effector T and regulatory T cells. BALB/c mice were exposed to two FA concentrations (1.38 mg/m3 and 5.36 mg/m3) for 4 h/day and 5 days/week for 2 weeks. FA-induced immune responses were examined by the production of cytokines, expression of mRNAs, and distributions of helper T cells and regulatory T cells. Moreover, expression of calcineurin and NFATs, regulatory T cell-related signalling proteins, were evaluated. FA exposure suppressed Th2-, Th1-, and Th17-related splenic cytokines in a dose-dependent manner. mRNA expression of splenic cytokines was also decreased by FA exposure, which correlated with decreased cytokine expression. In parallel, FA exposure promoted T cell differentiation into regulatory T cells in a dose-dependent manner supported by the expression of calcineurin and NFAT1. Taken together, our results indicated that FA exposure increases the number of regulatory T cells via calcineurin-NFAT signalling, thereby leading to effector T cell activity suppression with decreased T cell-related cytokine secretion and mRNA expression. These findings provide insight into the mechanisms underlying the adverse effects of FA and accordingly have general implications for human health, particularly in occupational settings.

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

Cited by 42 publications

References 61 publications

Toxic metal exposure as a possible risk factor for COVID-19 and other respiratory infectious diseases

Toxic metal exposure as a possible risk factor for COVID-19 and other respiratory infectious diseases

Chronic arsenic exposure induces the time-dependent modulation of inflammation and immunosuppression in spleen

Formaldehyde exposure induces regulatory T cell-mediated immunosuppression via calcineurin-NFAT signalling pathway

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