کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2595842 1562367 2011 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A single mid-gestation exposure to TCDD yields a postnatal autoimmune signature, differing by sex, in early geriatric C57BL/6 mice
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
A single mid-gestation exposure to TCDD yields a postnatal autoimmune signature, differing by sex, in early geriatric C57BL/6 mice
چکیده انگلیسی

We recently observed an autoimmune profile in 24-week-old C57BL/6 mice that received a 2.5 or 5.0 μg/kg mid-gestation dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) ( Mustafa et al., 2008). The clinical signs were consistent with a lupus-like syndrome and included: increased autoantibody levels, renal IgG and C3 immune complex deposition with associated inflammation, and increased peripheral Vβ+ T cells. No studies currently exist following the progression of such disease into middle or advanced ages, when human autoimmune diseases may manifest. Therefore in the present study, littermates of mice from the previous 24 week prenatal TCDD study were allowed to age to 48 weeks, considered early geriatric in mice. Similarities and differences in the disease profile based on age and sex were observed. Peripheral autoreactive Vβ+ T cells were increased in both sexes at 48 weeks, in contrast to males only at 24 weeks. Activated T cells from 48-week-old prenatal TCDD females over-produced the pro-inflammatory cytokine IFN-γ while males over-produced IL-10, effects again not seen at 24 weeks. Splenic transitional-2 B cells (CD21intCD24hi) were increased in males while transitional-1 B cells (CD23neg CD1neg) were increased in females at 48 weeks. Autoantibodies to cardiolipin and CD138+ spleen plasma cells were significantly increased in the aged males but not females. Anti-IgG and anti-C3 immune complex renal deposition were also significantly increased in the prenatal TCDD males but not females. These selective changes in the aged male mice may be noteworthy, in that the prevalence of SLE in humans shifts dramatically toward males with aging. The collective findings in aged mice suggest that prenatal TCDD permanently biases the postnatal immune response in C57BL/6 mice toward autoimmunity, and support a significant B cell component to the induced renal autoimmune disease.


► Prenatal TCDD altered the postnatal immune system, and differently so based on sex.
► Immune dysregulation affected both T and B cells, phenotypically and functionally.
► Prenatal TCDD caused a lupus-like autoimmune phenotype.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volume 290, Issues 2–3, 18 December 2011, Pages 156–168
نویسندگان
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