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Immune complexes inhibit IL-1 secretion and inflammasome activation
John R Janczy1, Ceren Ciraci2, Stefanie Haasken2
1Graduate Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, IA 52242; Inflammation Program, University of Iowa Carver College of Medicine, Iowa City, IA 52242;
Journal of Immunology (Baltimore, Md. : 1950)
|October 17, 2014
Summary
IgG immune complexes suppress inflammasome activation, reducing IL-1α and IL-1β secretion. This mechanism inhibits CD4(+) T cell differentiation and adaptive immune responses.
Area of Science:
- Immunology
- Innate Immunity
- Adaptive Immunity
Background:
- IgG immune complexes modulate APC-driven immune responses.
- The effect of IgG immune complexes on inflammasome activation is unknown.
Purpose of the Study:
- To investigate how IgG immune complexes affect inflammasome-dependent innate immune responses.
- To elucidate the mechanism of inflammasome inhibition by IgG immune complexes.
Main Methods:
- Studied IL-1α and IL-1β secretion in response to IgG immune complexes.
- Investigated inflammasome activation and assembly using NLR P3, NLRC4, and AIM2 agonists.
- Administered antigen as immune complexes in an in vivo model of allergic airway disease.
Main Results:
- IgG immune complexes suppress IL-1α and IL-1β secretion by inhibiting inflammasome activation.
- Immune complex ligation of FcγRs prevents inflammasome complex assembly.
- In vivo, IgG immune complexes inhibit adaptive immune responses in an NLRP3-dependent allergic airway disease model.
Conclusions:
- IgG immune complexes suppress innate immune responses by inhibiting inflammasome activation.
- This suppression impacts CD4(+) T cell differentiation, crucial for adaptive immunity.
- Reveals a novel regulatory mechanism for T cell differentiation involving immune complexes and APCs.
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