Interleukin-33 primes mast cells for activation by IgG immune complexes.
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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3469528?pdf=render |
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| author | Shinjiro Kaieda Jun-Xia Wang Ruslan Shnayder Nadia Fishgal Hillary Hei Richard T Lee Richard L Stevens Peter A Nigrovic |
| author_facet | Shinjiro Kaieda Jun-Xia Wang Ruslan Shnayder Nadia Fishgal Hillary Hei Richard T Lee Richard L Stevens Peter A Nigrovic |
| author_sort | Shinjiro Kaieda |
| collection | DOAJ |
| description | 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 FcγRIII, 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 FcγRIII-driven production of critical arthritogenic mediators including IL-1β and CXCL2. This "priming" effect was associated with mRNA accumulation rather than altered expression of Fcγ 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. |
| first_indexed | 2024-12-22T01:38:07Z |
| format | Article |
| id | doaj.art-6c3e5aa31d754a80889cd7613f7c7622 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T01:38:07Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-6c3e5aa31d754a80889cd7613f7c76222022-12-21T18:43:18ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01710e4725210.1371/journal.pone.0047252Interleukin-33 primes mast cells for activation by IgG immune complexes.Shinjiro KaiedaJun-Xia WangRuslan ShnayderNadia FishgalHillary HeiRichard T LeeRichard L StevensPeter A NigrovicMast 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 FcγRIII, 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 FcγRIII-driven production of critical arthritogenic mediators including IL-1β and CXCL2. This "priming" effect was associated with mRNA accumulation rather than altered expression of Fcγ 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.http://europepmc.org/articles/PMC3469528?pdf=render |
| spellingShingle | Shinjiro Kaieda Jun-Xia Wang Ruslan Shnayder Nadia Fishgal Hillary Hei Richard T Lee Richard L Stevens Peter A Nigrovic Interleukin-33 primes mast cells for activation by IgG immune complexes. PLoS ONE |
| title | Interleukin-33 primes mast cells for activation by IgG immune complexes. |
| title_full | Interleukin-33 primes mast cells for activation by IgG immune complexes. |
| title_fullStr | Interleukin-33 primes mast cells for activation by IgG immune complexes. |
| title_full_unstemmed | Interleukin-33 primes mast cells for activation by IgG immune complexes. |
| title_short | Interleukin-33 primes mast cells for activation by IgG immune complexes. |
| title_sort | interleukin 33 primes mast cells for activation by igg immune complexes |
| url | http://europepmc.org/articles/PMC3469528?pdf=render |
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