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* Department of Pathology and Experimental Medicine,
Department of Orthopaedic and Neuro-Musculoskeletal Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan;
Laboratory for Signal Network, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan;
Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, Kumamoto, Japan; and
¶ Department of Pathology and Experimental Medicine, Graduate School of Medical, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
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-
, and TNF-
. 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-, and TNF- 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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by grants from the Ministry of Education, Science, Sports and Culture, and the Ministry of Health and Welfare, Japan.
2 Address correspondence and reprint requests to Dr. Akihiro Matsukawa, Department of Pathology and Experimental Medicine, Graduate School of Medical, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan, 2-5-1, Shikata, Okayama 700-8558, Japan. E-mail address: amatsu{at}md.okayama-u.ac.jp
3 Abbreviations used in this paper: SOCS, suppressor of cytokine signaling; CLP, cecal ligation and puncture; WT, wild type; TSA, tryptose soy agar; APF, aminophenyl fluorescein; MPO, myeloperoxidase; BUN, blood urea nitrogen; MOF, multiple organ failure; Tg, transgenic.
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  Y. Ishida, T. Hayashi, T. Goto, A. Kimura, S. Akimoto, N. Mukaida, and T. Kondo Essential Involvement of CX3CR1-Mediated Signals in the Bactericidal Host Defense during Septic Peritonitis J. Immunol., September 15, 2008; 181(6): 4208 - 4218. [Abstract] [Full Text] [PDF]
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