Developmental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin alters postnatal T cell phenotypes and T cell function and exacerbates autoimmune lupus in 24-week-old SNF1 mice.

Developmental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin alters postnatal T cell phenotypes and T cell function and exacerbates autoimmune lupus in 24-week-old SNF1 mice.
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DOI:
10.1002/bdra.20603
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发表时间:
2009-10
影响因子:
--
通讯作者:
Gogal, Robert M., Jr.
Gogal, Robert M., Jr.
中科院分区:
医学4区
文献类型:
--
作者:
Mustafa, Amjad;Holladay, Steven D.;Goff, Matthew;Witonsky, Sharon;Kerr, Richard;Weinstein, Danielle A.;Karpuzoglu-Belgin, Ebru;Gogal, Robert M., Jr.

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Untreated, more than 95% of female SWR × NZB: F1 (SNF1) mice spontaneously develop a fatal lupus-like glomerulonephritis by 8 months-of-age, while disease onset in males is much slower. Timed-pregnant SNF1 mice (10/treatment) were exposed to TCDD on gestational day (GD) 12 by oral maternal gavage with 0, 40 or 80 μg/kg TCDD. Offspring of the TCDD-exposed dams showed numerous alterations in T lineage cells at 24 weeks-of-age. Females but not males showed decreased CD4+8+ and increased CD4−8− thymocytes. Females also showed increased autoreactive CD4+Vβ17a+ axillary and inguinal lymph node T cells. Con-A stimulated splenocytes from prenatal TCDD-treated mice produced decreased IL-17 in the females while males showed increased IL-2 and IFN-γ, and diminished IL-4. Mitogen-stimulated pan-lymphoproliferative responses were significantly increased across sex by TCDD. Anti-IgG and anti-C3 immune complex deposition in kidneys was present in the males after TCDD, and visibly worsened in females. Developmental TCDD exposure can permanently alter T lymphopoiesis in autoimmune-prone SNF1 mice. The alteration profile is beyond the classic immune suppression response, to also include exacerbation and induction of a lupus-like autoimmune disease.
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