title: IgE regulates T helper cell differentiation through FcgammaRIII 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-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.
authors.affiliation: Committee on Immunology, University of Chicago, 5841 S. Maryland, Chicago, IL 60637, USA. s-blink@northwestern.edu
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Blink
authors.forename: Yang-Xin
authors.initials: YX
authors.lastname: Fu
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics; D007073:Immunoglobulin E / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D008233:Lymphotoxin-alpha / Q000235:genetics; D053308:Lymphotoxin-beta / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011940:Receptor Aggregation; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D016207:Cytokines; C485700:Fcgr3 protein, mouse; D018398:Homeodomain Proteins; D008233:Lymphotoxin-alpha; D053308:Lymphotoxin-beta; D017452:Receptors, IgG; C064658:RAG-1 protein; D007073:Immunoglobulin E