IgE regulates T helper cell differentiation through FcgammaRIII mediated dendritic cell cytokine modulation.
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.
Blink
Sarah E
SE
Committee on Immunology, University of Chicago, 5841 S. Maryland, Chicago, IL 60637, USA. s-blink@northwestern.edu
Fu
Yang-Xin
YX
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
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