Involvement of CD300a Phosphatidylserine Immunoreceptor in Aluminum Salt Adjuvant–Induced Th2 Responses

Abstract

Aluminum salt (alum) has been widely used for vaccinations as an adjuvant. Alum not only enhances immunogenicity but also induces Th2 cell immune responses. However, the mechanisms of how alum enhances Th2 cell immune responses have been controversial. In an experimental allergic airway inflammation model, in which alum in conjunction with OVA Ag was i.p. injected for immunization, we found that apoptotic cells and inflammatory dendritic cells (iDC) expressing CD300a, an inhibitory immunoreceptor for phosphatidylserine (PS), significantly increased in number in the peritoneal cavity after the immunization. In contrast, apoptotic cells and iDCs were scarcely observed in the peritoneal cavity after injection of OVA alone. In CD300a-deficient mice, eosinophil infiltration in bronchoalveolar lavage fluid, serum IgE levels, and airway hyperreactivity were significantly decreased after immunization with alum plus OVA compared with wild-type mice. In vitro, iDCs purified from CD300a-deficient mice after the immunization induced significantly less IL-4 production from OT-II naive CD4+ T cells after coculture with OVA Ag. CD300a expressed on iDCs bound PS on apoptotic cells in the peritoneal cavity after injection of OVA plus alum. Blocking CD300a interaction with PS by injection of a neutralizing anti-CD300a Ab resulted in inhibition of the development of allergic airway inflammation. These results suggest that CD300a is involved in alum-induced Th2 skewing.

Leukocyte CD300a Contributes to the Resolution of Murine Allergic Inflammation

“…and then aerosolchallenged with OVA to induce allergic airway inflammation (23). In this model of airway AI, the CD300a 2/2 mice had less inflammation (23). Differences between results presented in that study and this report are likely related to differences in the route of sensitization, experimental models, and mouse strains.…”

“…Our results in this study on CD300a-mediated inhibition of AI in BALB/c mice are in contrast, in part, with a published report in C57BL6 CD300a 2/2 mice that were sensitized with OVA-alum i.p. and then aerosolchallenged with OVA to induce allergic airway inflammation (23). In this model of airway AI, the CD300a 2/2 mice had less inflammation (23).…”

Serum Metabolomics Analysis of Asthma in Different Inflammatory Phenotypes: A Cross-Sectional Study in Northeast China

“…Different from PCs, lysophosphatidylcholines (LysoPCs) have been reported to display a reduced level in experiment asthmatic mice and may act as immune suppressors [ 44 ]. In addition, phosphatidylserine (PS) was once considered to play an important role in Th2 induction and airway hyperreactivity [ 45 ], despite its regulatory effect on mast cells being converse to the above [ 46 ]. The distinct changing pattern for PCs, LysoPCs, and PSs indicates that there exist different roles of phospholipids homologues in the pathogenesis of asthma.…”

Positive and Negative Signals in Mast Cell Activation

“…Surprisingly, an opposite picture was seen in an experimental allergic airway inflammation model induced by alum with ovalbumin. In CD300a-deficient mice, eosinophil infiltration, serum IgE levels, and airway hyper-reactivity were significantly decreased after challenge [63], possibly because dendritic cells in the CD300a-deficient mice produced less IL-4.…”