In Vitro Induction of Mucosa-Type Dendritic Cells by All-Trans Retinoic Acid

Abstract

Efficient induction of mucosal immunity usually employs nasal or oral vaccination while parenteral immunization generally is ineffective at generating mucosal immune responses. This relates to the unique ability of resident mucosal dendritic cells (DC) to induce IgA switching and to imprint mucosa-specific homing receptors on lymphocytes. Based on the well-established plasticity of the DC system, this study sought to investigate whether peripheral DC could be modulated toward “mucosa-type” DC by treatment with immunomodulatory, and therefore potentially adjuvant-like, factors. In this study, we show that monocyte-derived DCs pretreated with the vitamin A derivative all-trans retinoic acid (RA) indeed acquired several attributes characteristic of mucosal DC: secretion of TGF-β and IL-6 and the capacity to augment mucosal homing receptor expression and IgA responses in cocultured lymphocytes. Addition of a TGF-β-neutralizing Ab to cocultures significantly inhibited α4β7 integrin, but not CCR9 mRNA expression by the lymphocytes. Both α4β7 integrin and CCR9 mRNA expression, but not IgA production, were suppressed in the presence of a RA receptor antagonist. None of the observed effects on the lymphocytes were influenced by citral, a retinal dehydrogenase inhibitor, arguing against a role for de novo-synthesized RA. Collectively, our findings identified a novel role for RA as a mucosal immune modulator targeting DC. Our results further demonstrate that DC can act as efficient carriers of RA at least in vitro. Consequently, RA targeting of DC shows potential for promoting vaccine-induced mucosal immune responses via a parenteral route of immunization.

Membrane markers of the immune cells in swine: an update

“…The mAb against murine 7 integrin and as well as the mAb against an epitope present on the human 4 7 dimeric molecule crossreact with 7 and 4 7 in swine [30,31]. Similar to murine studies, retinoic acid also mediates the induction of 4 7 on porcine lymphocytes [186].…”

Lymph Node Stromal Cells Support Dendritic Cell-Induced Gut-Homing of T Cells

“…Compatible with this are the reported observations that uptake and presentation of RA to T cells can occur by DCs upon preincubation with RA. This process did not involve newly formed RA, because RALDH blockade did not affect induction of ␣ 4 ␤ 7 and CCR9 expression on T cells (39). Similarly, a cell-cell interaction between MLN stromal cells and mucosal DCs might be required for the transfer of RA to mucosal DCs.…”

The identification and enumeration of dendritic cell populations from individual mouse spleen and Peyer's patches using flow cytometric analysis

“…However, the authors' used the DC properties of low buoyant density and adherence to glass to isolate and enrich for DCs (14). A variety of factors may influence the number of DCs in a tissue or animal at a given time, including infection, chronic disease states such as diabetes, hormones such as estradiol, nutrients such as vitamins A and D, as well as others (15)(16)(17)(18)(19)(20). However, previous methods used to analyze DCs have used enrichment techniques from pooled samples, either multiple tissue or animal sources, to obtain sufficient numbers of cells for analysis leading to potentially high variability and inaccurate DC number assessments.…”