論文 - 詳細
| RRC ID | 48851 |
|---|---|
| 著者 | Uchiyama R, Yonehara S, Taniguchi S, Ishido S, Ishii KJ, Tsutsui H. |
| タイトル | Inflammasome and Fas-Mediated IL-1β Contributes to Th17/Th1 Cell Induction in Pathogenic Bacterial Infection In Vivo. |
| ジャーナル | J Immunol |
| Abstract |
CD4+ Th cells play crucial roles in orchestrating immune responses against pathogenic microbes, after differentiating into effector subsets. Recent research has revealed the importance of IFN-γ and IL-17 double-producing CD4+ Th cells, termed Th17/Th1 cells, in the induction of autoimmune and inflammatory diseases. In addition, Th17/Th1 cells are involved in the regulation of infection caused by the intracellular bacterium Mycobacterium tuberculosis in humans. However, the precise mechanism of Th17/Th1 induction during pathogen infection is unclear. In this study, we showed that the inflammasome and Fas-dependent IL-1β induces Th17/Th1 cells in mice, in response to infection with the pathogenic intracellular bacterium Listeria monocytogenes In the spleens of infected wild-type mice, Th17/Th1 cells were induced, and expressed T-bet and Rorγt. In Pycard-/- mice, which lack the adaptor molecule of the inflammasome (apoptosis-associated speck-like protein containing a caspase recruitment domain), Th17/Th1 induction was abolished. In addition, the Fas-mediated IL-1β production was required for Th17/Th1 induction during bacterial infection: Th17/Th1 induction was abolished in Fas-/- mice, whereas supplementation with recombinant IL-1β restored Th17/Th1 induction via IL-1 receptor 1 (IL-1R1), and rescued the mortality of Fas-/- mice infected with Listeria IL-1R1, but not apoptosis-associated speck-like protein containing a caspase recruitment domain or Fas on T cells, was required for Th17/Th1 induction, indicating that IL-1β stimulates IL-1R1 on T cells for Th17/Th1 induction. These results indicate that IL-1β, produced by the inflammasome and Fas-dependent mechanisms, contributes cooperatively to the Th17/Th1 induction during bacterial infection. This study provides a deeper understanding of the molecular mechanisms underlying Th17/Th1 induction during pathogenic microbial infections in vivo. |
| 巻・号 | 199(3) |
| ページ | 1122-1130 |
| 公開日 | 2017-8-1 |
| DOI | 10.4049/jimmunol.1601373 |
| PII | jimmunol.1601373 |
| PMID | 28674179 |
| MeSH | Animals Apoptosis Regulatory Proteins / deficiency Apoptosis Regulatory Proteins / genetics Apoptosis Regulatory Proteins / metabolism CARD Signaling Adaptor Proteins Cell Differentiation Inflammasomes / immunology* Interleukin-1beta / administration & dosage Interleukin-1beta / immunology* Listeria monocytogenes / immunology* Listeria monocytogenes / pathogenicity Listeriosis / immunology* Mice Mice, Inbred C57BL Mice, Knockout Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism Receptors, Interleukin-1 Type I / genetics Receptors, Interleukin-1 Type I / immunology Spleen / immunology T-Box Domain Proteins / genetics T-Box Domain Proteins / metabolism Th1 Cells / immunology* Th17 Cells / immunology* fas Receptor / deficiency fas Receptor / genetics fas Receptor / metabolism* |
| IF | 4.886 |
| 引用数 | 11 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC00144 |