Overexpression of suppressor of cytokine signaling-5 in T cells augments innate immunity during septic peritonitis
| Autor: | Masato Kubo, Seiji Okada, Kosuke Numata, Katsumasa Takagi, Akihiro Matsukawa, Hiroshi Mizuta, Takaaki Ito, Hiroyuki Watanabe |
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| Rok vydání: | 2006 |
| Předmět: |
CD4-Positive T-Lymphocytes
Adoptive cell transfer Neutrophils Transgene medicine.medical_treatment T-Lymphocytes Immunology Mice Transgenic Suppressor of Cytokine Signaling Proteins Biology Peritonitis Mice Sepsis medicine Immunology and Allergy SOCS5 Animals IL-2 receptor Innate immune system Macrophages Molecular biology Adoptive Transfer In vitro Immunity Innate Mice Inbred C57BL Chemotaxis Leukocyte Cytokine Signal transduction |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 177(12) |
| ISSN: | 0022-1767 |
| Popis: | Suppressors of cytokine signaling (SOCS) proteins are negative regulators of cytokine signaling by inhibiting the JAK-STAT signal transduction pathway, but their role in innate immunity remains to be investigated. In the present study, we demonstrate that overexpression of SOCS5 in T cells augments innate immunity during septic peritonitis induced by cecal ligation and puncture (CLP). Mice with a cell-specific overexpression of SOCS5 in T cells (SOCS5 transgenic (Tg)) were resistant to the lethality relative to the wild-type (WT) mice. This was most likely due to the enhanced innate immunity in SOCS5Tg mice, as bacterial burden in SOCS5Tg mice was significantly lower than WT mice. Accumulation of neutrophils and macrophages was augmented in SOCS5Tg mice, an event that was accompanied by increased peritoneal levels of IL-12, IFN-γ, and TNF-α. In vitro bactericidal activities of macrophages and neutrophils were enhanced in SOCS5Tg mice. Both neutrophils and macrophages from WT mice adopted enhanced bacterial killing activity when cocultured with CD4+ T cells from SOCS5Tg mice, relative to CD4+ T cells from WT mice. Adoptive transfer of SOCS5Tg-CD4+ T cells into T- and B cell-deficient RAG-2−/− mice resulted in augmented leukocyte infiltration and increased peritoneal levels of IL-12, IFN-γ, and TNF-α after CLP, as compared with the controls. Furthermore, CLP-induced bacterial burden in RAG-2−/− mice harboring SOCS5Tg-CD4+ T cells was significantly reduced relative to the controls. These findings provide evidence that intervention of SOCS5 expression in T cells affects innate immunity, which highlight a novel role of T cells during sepsis. |
| Databáze: | OpenAIRE |
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