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

• Published in: Cellular immunology Vol. 264; no. 1; pp. 54 - 60
• Main Authors: Blink, Sarah E, Fu, Yang-Xin
• Format: Journal Article
• Language: English
• Published: Netherlands 2010
• Subjects: Animals; Cell Differentiation; Cells, Cultured; Cytokines - genetics; Cytokines - metabolism; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - pathology; Homeodomain Proteins - genetics; Immunoglobulin E - blood; Immunoglobulin E - genetics; Immunoglobulin E - metabolism; Lung - metabolism; Lymphotoxin-alpha - genetics; Lymphotoxin-beta - genetics; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptor Aggregation; Receptors, IgG - genetics; Receptors, IgG - immunology; Receptors, IgG - metabolism; Spleen - metabolism; Th1 Cells - immunology; Th1 Cells - metabolism; Th1 Cells - pathology; Th2 Cells - immunology; Th2 Cells - metabolism; Th2 Cells - pathology
• ISSN: 1090-2163
• DOI: 10.1016/j.cellimm.2010.04.011

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-crosslinking 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 FcgammaRIII 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 FcgammaRIII on dendritic cells.