IgE regulates T helper cell differentiation through FcγRIII mediated dendritic cell cytokine modulation

Abstract

Asthma and allergy are characterized by dysregulation of inflammatory responses toward Th2 responses and high serum levels of IgE. IgE plays a role in the effector phase by triggering the degranulation of mast cells after antigen-cross-linking but its role in the induction of helper T cell differentiation is unknown. We have previously shown lymphotoxin is required for maintaining physiological levels of serum IgE which minimize spontaneous Th1-mediated airway inflammation, suggesting a physiological role for IgE in the regulation of T helper cell differentiation. We describe the mechanism in which IgE modulates inflammation by regulating dendritic cell cytokine production. Physiological levels of IgE suppress IL-12 production in the spleen and lung, suggesting IgE limits Th1 responses in vivo. IgE directly stimulates dendritic cells through FcγRIII to suppress IL-12 in vitro and influences APC to skew CD4+ T cells toward Th2 differentiation. We demonstrate a novel role for IgE in regulating differentiation of adaptive inflammatory responses through direct interaction with FcγRIII on dendritic cells.

Asthma phenotypes and IgE responses

“…In addition, IgE can bind to other receptors, such as galectin-3 and FcγRIII. Whereas IgE-FcγRIII ligation on DCs has been shown in mice to promote Th2 responses through inhibition of IL-12 production [27], the role of these alternate receptors for IgE responses in human asthma remains unknown.…”

Convergence of two major pathophysiologic mechanisms in nasal polyposis: Immune response to Staphylococcus aureus and airway remodeling

“…This “flood” of polyclonal IgE fosters the acquired immune response via dendritic cell FcεRI and Fcγ receptors and, consequently, a Th2 response [39]. …”

Lung dendritic cells at the innate-adaptive immune interface

“…It was shown previously that IgE stimulates DCs directly through Fc␥RIII to suppress IL-12 production in vitro and influences APCs to skew CD4 ϩ T cells toward Th2 differentiation. Blink and Fu [154] demonstrated recently a novel role for IgE in regulating differentiation of adaptive immune responses through direct interaction with Fc␥RIII on DCs. In a different study, pDCs from patients with asthma were shown to secrete significantly less type I IFN upon exposure to influenza A virus, and secretion was inversely correlated with serum IgE levels [155].…”