Humoral Immune Response Modulation by Aryl hydrocarbon Receptor Activation (AhR) in CD11c+ Cells: Exploring Gender-specific and Ligand-dependent Effects on Antibody Responses in Mice

• Published in: The Journal of immunology (1950) 2018-05, Vol.200 (1_Supplement), p.107-107.14
• Main Authors: Kreitinger, Joanna, Shepherd, Celine Ann Beamer, Shepherd, David M.
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.200.Supp.107.14

Modulation of antibody responses is often a summation of effects on B cells, helper T cells, and dendritic cells (DCs). All three of these immune cells express AhR, a ligand-activated transcription factor with endogenous and exogenous ligands known to modulate immune responses. Importantly, antibody responses are keenly sensitive to AhR activation by TCDD, its prototypical ligand and common environmental pollutant. However, the specific contribution of AhR activation in DCs has not yet been defined, particularly in the context of gender-specific and ligand-dependent effects. We aimed to determine the effects of AhR activation in DCs by endogenous and exogenous ligands on OVA-specific antibody responses in mice. Specifically, we hypothesized that AhR activation in DCs alone suppresses antigen-specific serum antibody production, selectively affecting different isotypes. To test this hypothesis, we used mice conditionally deficient of AhR in CD11c+ DCs (AHRCD11c). Control (AhRd) and AHRCD11c mice were treated with vehicle, ITE or TCDD via oral gavage, and subsequently immunized i.p. with whole OVA/adjuvant to induce a systemic, antigen-specific humoral response. One week later, AhRd mice showed significantly reduced OVA-specific IgM and IgG2a titers while IgA was significantly increased; effects that were ameliorated in AhRCD11c mice. Interestingly, TCDD-induced IgA increases were both AhR- and gender-dependent with female mice showing increased IgA production. Collectively, these results demonstrate that DCs contribute to, but are not wholly responsible for, AhR-mediated effects on antigen-specific serum antibody generation. Research supported by ES013784 (DMS) and AAI Careers in Immunology Fellowship (JMK).