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Di-(2-ethylhexyl) phthalate adjuvantly induces imbalanced humoral immunity in ovalbumin-sensitized BALB/c mice ascribing to T follicular helper cells hyperfunction.
- Source :
-
Toxicology [Toxicology] 2014 Oct 03; Vol. 324, pp. 88-97. Date of Electronic Publication: 2014 Aug 02. - Publication Year :
- 2014
-
Abstract
- Di-(2-ethylhexyl) phthalate (DEHP) has been considered as a widespread environmental persistent organic pollutant and its potential concern on human health is raised by previous studies. In particular, children are more likely to be exposed to DEHP through gastrointestinal route and consequently are more susceptible to DEHP hazards. Some reports have uncovered a positive association between DEHP exposure and an increased prevalence of allergic diseases in infants and juveniles. Allergy is a hypersensitive reaction rooted in imbalanced humoral immunity. T follicular helper cell (Tfh), an important CD4(+) Th cell subset, until recently has been identified as a key player in humoral immune response by modifying B cells functions. Tfh cells are therefore perceived as the therapeutic target of immune disorders. In the present study, focusing on the newly confirmed Tfh cells, we examined the effects of DEHP on humoral immunity and investigated the underlying mechanisms. Using ovalbumin (OVA) sensitization weanling mice model under the condition of gastrointestinal exposure to DEHP, we found that DEHP acted as an immunoadjuvant to augment OVA-specific IgE and IgG1 production, amplified germinal center formation in lymphoid nodule, as well as stimulated the expansion of CD4(+)CXCR5(+)ICOS(+)/CD4(+)CXCR5(+)PD-1(+) Tfh cells and CD19(+)CD138(+)GL7(+) plasma cells. Based on the results of immune adoptive transfusion, DEHP-related anaphylactic response was ascribed to Tfh cells hyperfunction directly. We further proved that DEHP gavage together with OVA sensitization adjuvantly promoted the synthesis of cytokines IL-21 and IL-4 and the expression of transcription factors Bcl-6 and c-Maf in Tfh cells. In conclusion, our study demonstrates that DEHP has adjuvant toxic effects on Tfh cells by synthesizing an excess of cytokines IL-21 and IL-4 via over-expression of transcription factors Bcl-6 and c-Maf, leading to an increasing secretion of allergy-related IgE and IgG1.<br /> (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
- Subjects :
- Administration, Oral
Adoptive Transfer
Animals
B-Lymphocytes drug effects
B-Lymphocytes immunology
Cell Proliferation drug effects
DNA-Binding Proteins metabolism
Diethylhexyl Phthalate administration & dosage
Disease Models, Animal
Environmental Pollutants administration & dosage
Germinal Center immunology
Germinal Center metabolism
Hypersensitivity blood
Hypersensitivity immunology
Immunoglobulin E blood
Immunoglobulin G blood
Interleukin-4 metabolism
Interleukins metabolism
Mice
Mice, Inbred BALB C
Proto-Oncogene Proteins c-bcl-6
Proto-Oncogene Proteins c-maf metabolism
Risk Assessment
Risk Factors
T-Lymphocyte Subsets immunology
T-Lymphocyte Subsets metabolism
T-Lymphocyte Subsets transplantation
T-Lymphocytes, Helper-Inducer immunology
T-Lymphocytes, Helper-Inducer metabolism
T-Lymphocytes, Helper-Inducer transplantation
Diethylhexyl Phthalate toxicity
Environmental Pollutants toxicity
Germinal Center drug effects
Hypersensitivity etiology
Immunity, Humoral drug effects
Lymphocyte Activation drug effects
Ovalbumin
T-Lymphocyte Subsets drug effects
T-Lymphocytes, Helper-Inducer drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1879-3185
- Volume :
- 324
- Database :
- MEDLINE
- Journal :
- Toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 25093321
- Full Text :
- https://doi.org/10.1016/j.tox.2014.07.011