Immune complexes inhibit interleukin-1 secretion and inflammasome activation

• Published in: The Journal of immunology (1950) Vol. 193; no. 10; pp. 5190 - 5198
• Main Authors: Janczy, John R., Ciraci, Ceren, Haasken, Stefanie, Iwakura, Yoichiro, Olivier, Alicia K., Cassel, Suzanne L., Sutterwala, Fayyaz S.
• Format: Journal Article
• Language: English
• Published: 15-10-2014
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1400628

Immunoglobulin G (IgG) immune complexes have been shown to modify immune responses driven by antigen presenting cells in either a pro- or anti-inflammatory direction depending upon the context of stimulation. However, the ability of immune complexes to modulate the inflammasome-dependent innate immune response is unknown. Here we show that IgG immune complexes suppress IL-1α and IL-1β secretion through inhibition of inflammasome activation. The mechanism by which this inhibition occurs is via immune complex ligation of activating Fcγ receptors (FcγR), resulting in prevention of both activation and assembly of the inflammasome complex in response to NLRP3, NLRC4, or AIM2 agonists.
In vivo
, administration of antigen in the form of an immune complex during priming of the immune response inhibited resultant adaptive immune responses in a NLRP3 dependent model of allergic airway disease. Our data reveal an unexpected mechanism regulating CD4
+
T cell differentiation, whereby immune complexes suppress inflammasome activation and the generation of IL-1α and IL-1β from antigen presenting cells, which are critical for the antigen-driven differentiation of CD4
+
T cells.