|
Academic/Biomedical Research
News & Jobs
|
|
|
|
|
|
|
|
|
|
|
|
|
Free Newsletters
Archive
My Subscriptions
News by Subject
News by Disease
News by Date
PLoS
Search News
Post Your News
JoVE
Job Seeker Login
Most Recent Jobs
Search Jobs
Post Resume
Career Fairs
Career Resources
For Employers
Regional News
US & Canada
Biotech Bay
Biotech Beach
Genetown
Pharm Country
BioCapital
BioMidwest
Bio NC
BioForest
Southern Pharm
BioCanada East
US Device
Europe
Asia
Company Profiles
Research Store
Research Events
Post an Event
Real Estate
Business Opportunities
|
|
|
|
PLoS By Category | Recent
PLoS Articles
|
|
Biotechnology - Immunology - Rheumatology
|
Interleukin-33 Primes Mast Cells for Activation by IgG Immune Complexes
Published:
Thursday, October 11, 2012
Author:
Shinjiro Kaieda et al.
by Shinjiro Kaieda, Jun-Xia Wang, Ruslan Shnayder, Nadia Fishgal, Hillary Hei, Richard T. Lee, Richard L. Stevens, Peter A. Nigrovic
Mast cells (MCs) are heterogeneous cells whose phenotype is modulated by signals received from the local microenvironment. Recent studies have identified the mesenchymal-derived cytokine IL-33 as a potent direct activator of MCs, as well as regulator of their effector phenotype, and have implicated this activity in the ability of mast cells to contribute to murine experimental arthritis. We explored the hypothesis that IL-33 enables participation of synovial MCs in murine K/BxN arthritis by promoting their activation by IgG immune complexes. Compared to wild-type (WT) control mice, transgenic animals lacking the IL-33 receptor ST2 exhibited impaired MC-dependent immune complex-induced vascular permeability (flare) and attenuated K/BxN arthritis. Whereas participation of MCs in this model is mediated by the activating IgG receptor Fc?RIII, we pre-incubated bone marrow-derived MCs with IL-33 and found not only direct induction of cytokine release but also a marked increase in Fc?RIII-driven production of critical arthritogenic mediators including IL-1ß and CXCL2. This “priming” effect was associated with mRNA accumulation rather than altered expression of Fc? receptors, could be mimicked by co-culture of WT but not ST2-/- MCs with synovial fibroblasts, and was blocked by antibodies against IL-33. In turn, WT but not ST2-/- MCs augmented fibroblast expression of IL-33, forming a positive feedback circuit. Together, these findings confirm a novel role for IL-33 as an amplifier of IgG immune complex-mediated inflammation and identify a potential MC-fibroblast amplification loop dependent on IL-33 and ST2.
More...
|
|
|
 |
|
|
|
|
|
|
|
|