Journal of Immunotoxicology最新文献

{"title":"Exposure to a mixture of 23 chemicals associated with unconventional oil and gas operations alters immune response to challenge in adult mice.","authors":"Colleen T O'Dell,&nbsp;Lisbeth A Boule,&nbsp;Jacques Robert,&nbsp;Steve N Georas,&nbsp;Sophia Eliseeva,&nbsp;B Paige Lawrence","doi":"10.1080/1547691X.2021.1965677","DOIUrl":"https://doi.org/10.1080/1547691X.2021.1965677","url":null,"abstract":"<p><p>The prevalence of unconventional oil and gas (UOG) operations raises concerns regarding the potential for adverse health outcomes following exposure to water tainted by mixtures of UOG associated chemicals. The potential effects that exposure to complex chemical mixtures has on the immune system have yet to be fully evaluated. In this study, effects on the immune system of adult mice exposed to a mixture of 23 chemicals that have been associated with water near active UOG operations were investigated. Female and male mice were exposed to the mixture <i>via</i> their drinking water for at least 8 weeks. At the end of the exposure, cellularity of primary and secondary immune organs, as well as an immune system function, were assessed using three different models of disease, i.e. house dust mite (HDM)-induced allergic airway disease, influenza A virus infection, and experimental autoimmune encephalomyelitis (EAE). The results indicated exposures resulted in different impacts on T-cell populations in each disease model. Furthermore, the consequences of exposure differed between female and male mice. Notably, exposure to the chemical mixture significantly increased EAE disease severity in females, but not in male, mice. These findings indicated that direct exposure to this mixture leads to multiple alterations in T-cell subsets and that these alterations differ between sexes. This suggested to us that direct exposure to UOG-associated chemicals may alter the adult immune system, leading to dysregulation in immune cellularity and function.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":" ","pages":"105-117"},"PeriodicalIF":3.3,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8782265/pdf/nihms-1766633.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39363470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In vitro</i> prediction of <i>in vivo</i> pseudo-allergenic response via MRGPRX2.","authors":"Linu M John,&nbsp;Charlotte M Dalsgaard,&nbsp;Claus B Jeppesen,&nbsp;Kilian W Conde-Frieboes,&nbsp;Katrine Baumann,&nbsp;Niels P H Knudsen,&nbsp;Per S Skov,&nbsp;Birgitte S Wulff","doi":"10.1080/1547691X.2021.1877375","DOIUrl":"https://doi.org/10.1080/1547691X.2021.1877375","url":null,"abstract":"<p><p>In development of peptide therapeutics, rodents are commonly-used preclinical models when screening compounds for efficacy endpoints in the early stages of discovery projects. During the screening process, some peptides administered subcutaneously to rodents caused injection site reactions manifesting as localized swelling. Screening by postmortem evaluations of injection site swelling as a marker for local subcutaneous histamine release, were conducted in rats to select drug candidates without this adverse effect. Histological analysis of skin samples revealed that the injection site reactions were concurrent with mast cell degranulation, resulting in histamine release. Mast cell activation can be mediated by MRGPRX2, a GPCR that induces a pseudo-allergenic immune response. The present study demonstrates that a commercially-available cell-based MRGPRX2 assay reliably identifies compounds that induce histamine release or localized edema in <i>ex vivo</i> human and rodent skin samples. <i>In vitro</i> screening was subsequently implemented using the MRGPRX2 assay as a substitute for postmortem injection site evaluation, thus achieving a significant reduction in animal use. Thus, in cases where injection site reactions are encountered during <i>in vivo</i> screening, to enable faster screening during the early drug discovery process, an MRGPRX2 <i>in vitro</i> assay can be used as an efficient, more ethical tool with human translational value for the development of safer pharmacotherapies for patients.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":" ","pages":"30-36"},"PeriodicalIF":3.3,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2021.1877375","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25356475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of inhaled anesthetic gases on immune status alterations in health care workers.","authors":"Ashraf Mahmoud Emara,&nbsp;Khaled Ali Alrasheedi,&nbsp;Salha Dihim Alrashidi,&nbsp;Rehab Mohamed Elgharabawy","doi":"10.1080/1547691X.2020.1869872","DOIUrl":"https://doi.org/10.1080/1547691X.2020.1869872","url":null,"abstract":"<p><p>The objective of this research was to evaluate consequences to the immune system of long-term exposure to waste anesthetic gases (WAG) by medical theater personnel. Two groups were recruited: (i) 60 healthy male controls; (ii) 120 medical professionals exposed to WAG, subdivided according to theater role, i.e. surgeons, surgical assistants (SA), anesthetists, anesthetic assistants (AA), nurses, and workers. Serum levels of fluoride, hexafluoroisopropanol (HFIP), total lymphocyte counts, as well as of CD3, CD4, and CD8 cells, CD4/CD8 ratios, and immunoglobulins IgA, IgG, IgM, and IgE were assayed. The results showed that fluoride and HFIP titers were significantly increased in anesthetists and AA compared with the other exposed groups. All exposed groups demonstrated significant elevation in lymphocyte count, CD4⁺ cell levels, CD4/CD8 ratios, as well as levels of IgE, IgM and IgG compared with the controls. With regard to the latter outcomes, a significant increase in IgE was seen in the surgeon, nurse, and worker groups compared with the other professions. Surgeons, anesthetists and AA exhibited higher IgM titers compared with their colleagues. Significantly higher IgG levels were identified in the SA, anesthetists, AA, and workers than in their nurses and surgeon coworkers. Of the six sub-groups, only the anesthetists and their assistants (AA) displayed a significant increase in CD4⁺ cells and CD4/CD8 ratios and a decrease of CD8⁺ cells compared with the controls. This spectrum of results suggests that variation exists in immunomodulatory responses to WAG exposure amongst hospital personnel.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":" ","pages":"13-22"},"PeriodicalIF":3.3,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2020.1869872","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25393319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adverse immunological responses against non-viral nanoparticle (NP) delivery systems in the lung.","authors":"Leonor de Braganca,&nbsp;G John Ferguson,&nbsp;Jose Luis Santos,&nbsp;Jeremy P Derrick","doi":"10.1080/1547691X.2021.1902432","DOIUrl":"https://doi.org/10.1080/1547691X.2021.1902432","url":null,"abstract":"<p><p>There is a large, unmet medical need to treat chronic obstructive pulmonary disease, asthma, idiopathic pulmonary fibrosis and other respiratory diseases. New modalities are being developed, including gene therapy which treats the disease at the DNA/RNA level. Despite recent innovations in non-viral gene therapy delivery for chronic respiratory diseases, unwanted or adverse interactions with immune cells, particularly macrophages, can limit drug efficacy. This review will examine the relationship between the design and fabrication of non-viral nucleic acid nanoparticle (NP) delivery systems and their ability to trigger unwanted immunogenic responses in lung tissues. NP formulated with peptides, lipids, synthetic and natural polymers provide a robust means of delivering the genetic cargos to the desired cells. However NP, or their components, may trigger local responses such as cell damage, edema, inflammation, and complement activation. These effects may be acute short-term reactions or chronic long-term effects like fibrosis, increased susceptibility to diseases, autoimmune disorders, and even cancer. This review examines the relationship between physicochemical properties, i.e. shape, charge, hydrophobicity, composition and stiffness, and interactions of NP with pulmonary immune cells. Inhalation is the ideal route of administration for direct delivery but inhaled NP encounter innate immune cells, such as alveolar macrophages (AM) and dendritic cells (DC), that perceive them as harmful foreign material, interfere with gene delivery to target cells, and can induce undesirable side effects. Recommendations for fabrication and formulation of gene therapies to avoid adverse immunological responses are given. These include fine tuning physicochemical properties, functionalization of the surface of NP to actively target diseased pulmonary cells and employing biomimetics to increase immunotolerance.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":" ","pages":"61-73"},"PeriodicalIF":3.3,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2021.1902432","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38875507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of a newly-developed cynomolgus macaque BiTE-mediated cytotoxic T-lymphocyte activity assay to various immunomodulatory agents <i>in vitro</i>.","authors":"Brendon Frank,&nbsp;Hao Guo,&nbsp;Hervé Lebrec,&nbsp;Xiaoting Wang","doi":"10.1080/1547691X.2021.1992687","DOIUrl":"https://doi.org/10.1080/1547691X.2021.1992687","url":null,"abstract":"<p><p>The immunotoxic potential of drug candidates is assessed through the examination of results from a variety of <i>in vitro</i> and <i>in vivo</i> immunophenotyping and functional study endpoints in pre-clinical studies. CD8⁺ cytotoxic T-lymphocyte (CTL) activity impairment by immunosuppressive agents is recognized to be a potentiating factor for decreased antiviral defense and increased cancer risk. A bi-specific T-cell engager (BiTE^®)-mediated CTL activity assay that applies to <i>ex vivo</i> experimentation in non-human primates in the context of toxicology studies was successfully developed and applied in cynomolgus monkey regulatory studies. While an <i>ex vivo</i> analysis conducted in the context of repeat-dose toxicology studies focuses on the long-term impact on CTL function, an <i>in vitro</i> assay with the same experimental design captures acute effects in the presence of the test article. Here, the <i>in vitro</i> assay was applied to a list of drugs with known clinical immunomodulatory impact to understand the applicability of the assay. The results showed this assay was sensitive to a wide range of immunosuppressants directly targeting cell-intrinsic signaling pathways in activated CTL. However, agents executing immuno-modulation through inhibiting cytokines/cytokine receptors, co-stimulatory molecules, and cell adhesion and migration pathways did not impair the CTL activity in this short-term <i>in vitro</i> culture. In addition, anti-PD-1/PD-L1 immune checkpoint blockers enhanced the CTL activity. Taken together, the results here demonstrate that in concordance with their mechanism of action, the <i>in vitro</i> BiTE^®-mediated CTL assay is applicable and sensitive to immunomodulatory agents acting <i>via</i> a variety of mechanisms.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":" ","pages":"154-162"},"PeriodicalIF":3.3,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39662554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epicutaneous challenge with protease allergen requires its protease activity to recall T_H2 and T_H17/T_H22 responses in mice pre-sensitized via distant skin.","authors":"Akira Ogasawara,&nbsp;Takuo Yuki,&nbsp;Toshiro Takai,&nbsp;Kyosuke Yokozeki,&nbsp;Asuka Katagiri,&nbsp;Yutaka Takahashi,&nbsp;Hiroo Yokozeki,&nbsp;David Basketter,&nbsp;Hitoshi Sakaguchi","doi":"10.1080/1547691X.2021.1968548","DOIUrl":"https://doi.org/10.1080/1547691X.2021.1968548","url":null,"abstract":"<p><p>Epicutaneous exposure to allergenic proteins is an important sensitization route for skin diseases like protein contact dermatitis, immunologic contact urticaria, and atopic dermatitis. Environmental allergen sources such as house dust mites contain proteases, which are frequent allergens themselves. Here, the dependency of T-helper (T_H) cell recall responses on allergen protease activity in the elicitation phase in mice pre-sensitized via distant skin was investigated. Repeated epicutaneous administration of a model protease allergen, i.e. papain, to the back skin of hairless mice induced skin inflammation, serum papain-specific IgE and T_H2 and T_H17 cytokine responses in the sensitization sites, and antigen-restimulated draining lymph node cells. In the papain-sensitized but not vehicle-treated mice, subsequent single challenge on the ear skin with papain, but not with protease inhibitor-treated papain, up-regulated the gene expression of T_H2 and T_H17/T_H22 cytokines along with cytokines promoting these T_H cytokine responses (TSLP, IL-33, IL-17C, and IL-23p19). Up-regulation of IL-17A gene expression and cells expressing RORγt occurred in the ear skin of the presensitized mice even before the challenge. In a reconstructed epidermal model with a three-dimensional culture of human keratinocytes, papain but not protease inhibitor-treated papain exhibited increasing transdermal permeability and stimulating the gene expression of TSLP, IL-17C, and IL-23p19. This study demonstrated that allergen protease activity contributed to the onset of cutaneous T_H2 and T_H17/T_H22 recall responses on allergen re-encounter at sites distant from the original epicutaneous sensitization exposures. This finding suggested the contribution of protease-dependent barrier disruption and induction of keratinocyte-derived cytokines to the recall responses.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":" ","pages":"118-126"},"PeriodicalIF":3.3,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39388912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Galangin ameliorates experimental autoimmune encephalomyelitis in mice via modulation of cellular immunity.","authors":"Kok-Tong Tan,&nbsp;Shiming Li,&nbsp;Lauren Panny,&nbsp;Chi-Chien Lin,&nbsp;Shih-Chao Lin","doi":"10.1080/1547691X.2021.1890863","DOIUrl":"https://doi.org/10.1080/1547691X.2021.1890863","url":null,"abstract":"<p><p>Multiple sclerosis (MS) causes neurologic disabilities that effect musculature, sensory systems, and vision. This is largely due to demyelination of nerve fibers caused by chronic inflammation. Corticosteroid treatments ameliorate symptoms of MS, but do not successfully cure the disease itself. In the current study, the application of galangin, a phytochemical flavonoid extracted from the ginger family of <i>Alpinis officinarum</i>, on experimental autoimmune encephalomyelitis (EAE; mouse model for MS) was explored. This study investigated prophylactic and therapeutic activity of the drug and mechanisms by which it acts. The results revealed that galangin at 40 and 80 mg/kg could lower the incidence rate of MS, and alleviate clinical/pathological manifestations. Mice administered galangin presented with less limb paralysis, lower levels of inflammatory cell infiltrates, and decreased demyelination compared to vehicle controls. Levels of CD4⁺IFNγ⁺ (T_H1) and CD4⁺IL-17A⁺ (T_H17) cells in the spinal cords of EAE mice administered galangin were reduced and both cell types were not capable of expansion. More surprisingly, galangin inhibited antigen presentation and cytokine production by dendritic cells (DC). Formation of cytokines like IL-6, IL-12, and IL-23 were significantly decreased due to galangin in co-culture models of DC and T-cells. Taken together, the data lead one to conclude that galangin could potentially be used as a potent immunoregulatory agent to alleviate clinical symptoms and reduce the prevalence of MS.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":" ","pages":"50-60"},"PeriodicalIF":3.3,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2021.1890863","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25519671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary advanced glycation end-products elicit toxicological effects by disrupting gut microbiome and immune homeostasis.","authors":"Yingjia Chen,&nbsp;Tai L Guo","doi":"10.1080/1547691X.2021.1959677","DOIUrl":"https://doi.org/10.1080/1547691X.2021.1959677","url":null,"abstract":"<p><p>The aging immune system is characterized by a low-grade chronic systemic inflammatory state (\"inflammaging\") marked by elevated serum levels of inflammatory molecules such as interleukin (IL)-6 and C-reactive protein (CRP). These inflammatory markers were also reported to be strong predictors for the development/severity of Type 2 diabetes, obesity, and COVID-19. The levels of these markers have been positively associated with those of advanced glycation end-products (AGEs) generated via non-enzymatic glycation and oxidation of proteins and lipids during normal aging and metabolism. Based on the above observations, it is clinically important to elucidate how dietary AGEs modulate inflammation and might thus increase the risk for aging-exacerbated diseases. The present narrative review discusses the potential pro-inflammatory properties of dietary AGEs with a focus on the inflammatory mediators CRP, IL-6 and ferritin, and their relations to aging in general and Type 2 diabetes in particular. In addition, underlying mechanisms - including those related to gut microbiota and the receptors for AGEs, and the roles AGEs might play in affecting physiologies of the healthy elderly, obese individuals, and diabetics are discussed in regard to any greater susceptibility to COVID-19.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"18 1","pages":"93-104"},"PeriodicalIF":3.3,"publicationDate":"2021-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9885815/pdf/nihms-1865814.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10636841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Organic dust-induced lung injury and repair: Bi-directional regulation by TNFα and IL-10.","authors":"T A Wyatt, M Nemecek, D Chandra, J M DeVasure, A J Nelson, D J Romberger, J A Poole","doi":"10.1080/1547691X.2020.1776428","DOIUrl":"10.1080/1547691X.2020.1776428","url":null,"abstract":"<p><p>Exposure to organic dust increases chronic airway inflammatory disorders. Effective treatment strategies are lacking. It has been reported that hog barn dust extracts (HDE) induce TNFα through protein kinase C (PKC) activation and that lung inflammation is enhanced in scavenger receptor A (SRA/CD204) knockout (KO) mice following HDE. Because interleukin (IL)-10 production can limit excessive inflammation, it was hypothesized here that HDE-induced IL-10 would require CD204 to effect inflammatory responses. C57BL/6 wild-type (WT), SRA KO, and IL-10 KO mice were intranasally challenged daily for 8 days with HDE and subsequently rested for 3 days with/without recombinant IL-10 (rIL-10) treatment. Primary peritoneal macrophages (PM) and murine alveolar macrophages (MH-S cells) were treated <i>in vitro</i> with HDE, SRA ligand (fucoidan), rIL-10, and/or PKC isoform inhibitors. HDE induced <i>in vivo</i> lung IL-10 in WT, but not SRA KO mice, and similar trends were demonstrated in isolated PM from same treated mice. Lung lymphocyte aggregates and neutrophils were elevated in <i>in vivo</i> HDE-treated SRA and IL-10 KO mice after a 3-d recovery, and treatment during recovery with rIL-10 abrogated these responses. <i>In vitro</i> rIL-10 treatment reduced HDE-stimulated TNFα release in MH-S and WT PM. In SRA KO macrophages, there was reduced IL-10 and PKC zeta (ζ) activity and increased TNFα following <i>in vitro</i> HDE stimulation. Similarly, blocking SRA (24 hr fucoidan pre-treatment) resulted in enhanced HDE-stimulated macrophage TNFα and decreased IL-10 and PKCζ activation. PKCζ inhibitors blocked HDE-stimulated IL-10, but not TNFα. Collectively, HDE stimulates IL-10 by an SRA- and PKCζ-dependent mechanism to regulate TNFα. Enhancing resolution of dust-mediated lung inflammation through targeting IL-10 and/or SRA may represent new approaches to therapeutic interventions.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"17 1","pages":"153-162"},"PeriodicalIF":2.4,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11238278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10770903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prenatal arsenic exposure interferes in postnatal immunocompetence despite an absence of ongoing arsenic exposure.","authors":"Mainak Chakraborty,&nbsp;Moumita Bhaumik","doi":"10.1080/1547691X.2020.1767238","DOIUrl":"https://doi.org/10.1080/1547691X.2020.1767238","url":null,"abstract":"<p><p>Arsenic (As) readily crosses the placenta and exposure of the fetus may cause adverse consequences later in life, including immunomodulation. In the current study, the question was asked how the immune repertoire might respond in postnatal life when there is no further As exposure. Here, pregnant mice (Balb/c [H-2^d]) were exposed to arsenic trioxide (As₂O₃) through their drinking water from time of conception until parturition. Their offspring, 4-week-old mice who had not been exposed again to As, were used for functional analyses of innate, humoral and cellular immunity. Compared to cells from non-As-exposed dam offspring, isolated peritoneal macro-phages (Mϕ) displayed no differences in T-cell stimulating ability. Levels of circulating IgG_2a but not IgG₁ were decreased in As-exposed dam offspring as compared to control offspring counterparts. Mixed-leukocyte reactions (MLR) indicated that CD4⁺ T-cells from the prenatal As-exposed mice were significantly less responsive to allogenic stimulation as evidenced by decreases in interferon (IFN)-γ and IL-2 production and in expression of CD44 and CD69 (but not CD25) activation markers. Interestingly, the Mϕ from the prenatal As-exposed mice were capable of stimulating normal allogenic T-cells, indicating that T-cells from these mice were refractory to allogenic signals. There was also a significant decrease in absolute numbers of splenic CD4⁺ and CD8⁺ T-cells due to prenatal As exposure (as compared to control). Lastly, the impaired immune function of the prenatal As-exposed mice was correlated with a very strong susceptibility to <i>Escherichia coli</i> infection. Taken together, the data from this study clearly show that <i>in utero</i> As exposure may continue to perpetuate a dampening effect on the immune repertoire of offspring, even into the early stages of postnatal life.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":" ","pages":"135-143"},"PeriodicalIF":3.3,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2020.1767238","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38044514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}