Journal Article

Effects of TCDD on the Fate of Naive Dendritic Cells

Jaishree Bankoti, Andrea Burnett, Severine Navarro, Andrea K. Miller, Ben Rase and David M. Shepherd

in Toxicological Sciences

Volume 115, issue 2, pages 422-434
Published in print June 2010 | ISSN: 1096-6080
Published online March 2010 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfq063
Effects of TCDD on the Fate of Naive Dendritic Cells

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The environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), causes immune suppression via activation of the aryl hydrocarbon receptor. Dendritic cells (DCs), the professional antigen-presenting cells in the immune system, are adversely affected by TCDD. We hypothesized that TCDD alters DC homeostasis, resulting in a loss of DCs in naive mice. To test this hypothesis, C57Bl/6 mice were gavaged with either vehicle or an immunosuppressive dose of TCDD (15 μg/kg). TCDD exposure decreased the frequency and number of splenic CD11chigh DCs on day 7 when compared with vehicle-treated controls. TCDD increased the expression of CD86 and CD54, while decreasing the frequency of splenic CD11chigh DCs expressing CD11a and major histocompatibility complex (MHC) class II. Moreover, TCDD selectively decreased the CD11chighCD8α33D1+ splenic DCs specialized at activating CD4+ T cells but did not affect the regulatory CD11chighCD8α+DEC205+ splenic DCs. TCDD did not alter the number or frequency of CD11clow splenic DCs but decreased their MHC class II and CD11a expression. Loss of splenic CD11chigh DCs was independent of Fas-mediated apoptosis and was not due to alterations in the numbers of common DC precursors in the bone marrow or their ability to generate steady-state DCs in vitro. Instead, increased CCR7 expression on CD11chigh DCs suggested involvement of a migratory event. Popliteal and brachial lymph node CD11c+ cells showed elevated levels of MHC class II and CD40 following TCDD exposure. Collectively, this study shows the presence of a TCDD-sensitive splenic DC subpopulation in naive mice, suggesting that TCDD may induce suppression of T-cell-mediated immunity by disrupting DC homeostasis.

Keywords: aryl hydrocarbon receptor; dendritic cells; immunotoxicity; TCDD; apoptosis; CCR7

Journal Article.  6909 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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