Effects of Dendritic Cell Subset Manipulation on Airway Allergy in a Mouse Model

Abstract

Background: Two major distinct subsets of dendritic cells (DCs) are arranged to regulate immune responses: DEC-205+ DCs drive Th1 polarization and 33D1+ DCs establish Th2 dominancy. Th1 polarization can be achieved either by depletion of 33D1+ DCs with a 33D1-specific monoclonal antibody (mAb) or by activation of DEC-205+ DCs via intraperitoneal injection of α-galactosylceramide (α-GalCer). We studied the effect of 33D1+ DC depletion or DEC-205+ DC activation in vivo using an established mouse model of allergic rhinitis (AR). Methods: Mice were injected intraperitoneally with OVA plus alum and challenged 4 times with daily intranasal administration of OVA. Immediately after the last challenge, allergic symptoms such as sneezing and nasal rubbing as well as the number of cells in the bronchoalveolar lavage fluid (BALF) and nasal lavage fluid (NALF) were counted. The levels of serum OVA-specific IgG1, IgG2a, and IgE were also determined by ELISA. Results: The allergic symptom scores were significantly decreased in 33D1+ DC-depleted or DEC-205+ DC-activated AR mice. The levels of OVA-specific IgG1, IgG2a, and IgE, and the number of NALF cells, but not BALF cells, were reduced in 33D1+ DC-depleted but not in DEC-205+ DC-activated AR mice. Moreover, the activated DEC-205+ DCs suppressed histamine release from IgE-sensitized mast cells, probably through IL-12 secretion. Conclusions: The manipulation of innate DC subsets may provide a new therapeutic strategy for controlling various allergic diseases by reducing histamine release from IgE-sensitized mast cells by driving the immune response towards Th1 dominancy via activation of DEC-205+ DCs in vivo.

Suppression of murine tumour growth through CD8+ cytotoxic T lymphocytes via activated DEC‐205+ dendritic cells by sequential administration of α‐galactosylceramide in vivo

“…injection of α ‐GalCer in BALB/c mice 14. Based on this finding, we examined whether α ‐GalCer also selectively stimulated DEC‐205 + DCs in the spleen cells of B6 mice.…”

“…Based on these findings, we questioned whether we could alter the conditions of the DEC‐205 + tolerogenic DCs within the Hepa1‐6‐1‐derived tumour into immunogenic DCs with higher expression levels of co‐stimulatory molecules using the external administration of α ‐galactosylceramide ( α ‐GalCer), a potent activator of DEC‐205 + DCs 14. In this study, we show for the first time that the growth of an ongoing Hepa1‐6‐1‐derived tumour mass was profoundly suppressed by internally induced Hepa1‐6‐1‐specific CD8 + CTLs but not by the activated invariant natural killer T (iNKT) cells through a sequential repetitive intraperitoneal (i.p.)…”

Recent Advances in Experimental Allergy

“…Murakami et al [47] investigated the role of DC subsets in an OVA-induced AR mouse model. Specifically, they assessed the effect DEC-205 + DCs, which drive Th1 polarization, and 33D1 + DCs, which establish Th2 dominancy.…”

Innate immunity and chronic rhinosinusitis: What we have learned from animal models

“…In Th2‐skewed inflammation, Th2 lymphocytes are a major source of IL‐4, IL‐5, and IL‐13. In mice, two subsets of dendritic cells have been identified: CD205+ dendritic cells (which elicit a Th1 polarization) and 33D1+ dendritic cells (which shift toward a Th2 phenotype) . Utilizing an OVA‐induced allergic nasal inflammatory model, this group hypothesized that shifting the dendritic response toward a Th1 subset would modulate allergic symptoms.…”

“…Utilizing an OVA‐induced allergic nasal inflammatory model, this group hypothesized that shifting the dendritic response toward a Th1 subset would modulate allergic symptoms. Through the depletion of 33D1+ dendritic cells using an anti‐33D1 antibody, as well as selective activation of CD205+ dendritic cells using the glycolipid antigen α‐GalCer, they reported a decrease in nasal symptoms such as rubbing and sneezing, as well as a decrease in inflammatory cell accumulation in nasal lavage fluid . The role of dendritic cells has been much more extensively studied in animal models of airway inflammation compared to sinonasal inflammation.…”