Hyperproduction of Proinflammatory Cytokines by WSX-1-Deficient NKT Cells in Concanavalin A-Induced Hepatitis

Atsushi Yamanaka, Shinjiro Hamano, Yoshiyuki Miyazaki, Kazunari Ishii, Atsunobu Takeda, Tak W. Mak, Kunisuke Himeno, Akihiko Yoshimura, Hiroki Yoshida

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

Administration of Con A induces liver injury that is considered to be an experimental model for human autoimmune or viral hepatitis, where immunopathology plays roles mediated by activated lymphocytes, especially NK1.1+ CD3+ NKT cells, and inflammatory cytokines, including IFN-γ and IL-4. In the present study we investigated the role of WSX-1, a component of IL-27R, in Con A-induced hepatitis by taking advantage of WSX-1 knockout mice. WSX-1-deficient mice were more susceptible to Con A treatment than wild-type mice, showing serum alanine aminotransferase elevation and massive necrosis in the liver. Although the development of NKT cells appeared normal in WSX-1 knockout mice, purified NKT cells from the knockout mice produced more IFN-γ and IL-4 than those from wild-type mice in response to stimulation with Con A both in vitro and in vivo. In addition, hyperproduction of proinflammatory cytokines, including IL-1, IL-6, and TNF-α, was observed in the knockout mice after Con A administration. These data revealed a novel role for WSX-1 as an inhibitory regulator of cytokine production and inflammation in Con A-induced hepatitis.

Original languageEnglish
Pages (from-to)3590-3596
Number of pages7
JournalJournal of Immunology
Volume172
Issue number6
DOIs
Publication statusPublished - Mar 15 2004

Fingerprint

Natural Killer T-Cells
Concanavalin A
Knockout Mice
Hepatitis
Cytokines
Interleukin-4
Liver
Alanine Transaminase
Interleukin-1
Interleukin-6
Theoretical Models
Necrosis
Lymphocytes
Inflammation
Wounds and Injuries
Serum

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Hyperproduction of Proinflammatory Cytokines by WSX-1-Deficient NKT Cells in Concanavalin A-Induced Hepatitis. / Yamanaka, Atsushi; Hamano, Shinjiro; Miyazaki, Yoshiyuki; Ishii, Kazunari; Takeda, Atsunobu; Mak, Tak W.; Himeno, Kunisuke; Yoshimura, Akihiko; Yoshida, Hiroki.

In: Journal of Immunology, Vol. 172, No. 6, 15.03.2004, p. 3590-3596.

Research output: Contribution to journalArticle

Yamanaka, A, Hamano, S, Miyazaki, Y, Ishii, K, Takeda, A, Mak, TW, Himeno, K, Yoshimura, A & Yoshida, H 2004, 'Hyperproduction of Proinflammatory Cytokines by WSX-1-Deficient NKT Cells in Concanavalin A-Induced Hepatitis', Journal of Immunology, vol. 172, no. 6, pp. 3590-3596. https://doi.org/10.4049/jimmunol.172.6.3590
Yamanaka, Atsushi ; Hamano, Shinjiro ; Miyazaki, Yoshiyuki ; Ishii, Kazunari ; Takeda, Atsunobu ; Mak, Tak W. ; Himeno, Kunisuke ; Yoshimura, Akihiko ; Yoshida, Hiroki. / Hyperproduction of Proinflammatory Cytokines by WSX-1-Deficient NKT Cells in Concanavalin A-Induced Hepatitis. In: Journal of Immunology. 2004 ; Vol. 172, No. 6. pp. 3590-3596.
@article{7cf199ef13f64df9a261686636905680,
title = "Hyperproduction of Proinflammatory Cytokines by WSX-1-Deficient NKT Cells in Concanavalin A-Induced Hepatitis",
abstract = "Administration of Con A induces liver injury that is considered to be an experimental model for human autoimmune or viral hepatitis, where immunopathology plays roles mediated by activated lymphocytes, especially NK1.1+ CD3+ NKT cells, and inflammatory cytokines, including IFN-γ and IL-4. In the present study we investigated the role of WSX-1, a component of IL-27R, in Con A-induced hepatitis by taking advantage of WSX-1 knockout mice. WSX-1-deficient mice were more susceptible to Con A treatment than wild-type mice, showing serum alanine aminotransferase elevation and massive necrosis in the liver. Although the development of NKT cells appeared normal in WSX-1 knockout mice, purified NKT cells from the knockout mice produced more IFN-γ and IL-4 than those from wild-type mice in response to stimulation with Con A both in vitro and in vivo. In addition, hyperproduction of proinflammatory cytokines, including IL-1, IL-6, and TNF-α, was observed in the knockout mice after Con A administration. These data revealed a novel role for WSX-1 as an inhibitory regulator of cytokine production and inflammation in Con A-induced hepatitis.",
author = "Atsushi Yamanaka and Shinjiro Hamano and Yoshiyuki Miyazaki and Kazunari Ishii and Atsunobu Takeda and Mak, {Tak W.} and Kunisuke Himeno and Akihiko Yoshimura and Hiroki Yoshida",
year = "2004",
month = "3",
day = "15",
doi = "10.4049/jimmunol.172.6.3590",
language = "English",
volume = "172",
pages = "3590--3596",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "6",

}

TY - JOUR

T1 - Hyperproduction of Proinflammatory Cytokines by WSX-1-Deficient NKT Cells in Concanavalin A-Induced Hepatitis

AU - Yamanaka, Atsushi

AU - Hamano, Shinjiro

AU - Miyazaki, Yoshiyuki

AU - Ishii, Kazunari

AU - Takeda, Atsunobu

AU - Mak, Tak W.

AU - Himeno, Kunisuke

AU - Yoshimura, Akihiko

AU - Yoshida, Hiroki

PY - 2004/3/15

Y1 - 2004/3/15

N2 - Administration of Con A induces liver injury that is considered to be an experimental model for human autoimmune or viral hepatitis, where immunopathology plays roles mediated by activated lymphocytes, especially NK1.1+ CD3+ NKT cells, and inflammatory cytokines, including IFN-γ and IL-4. In the present study we investigated the role of WSX-1, a component of IL-27R, in Con A-induced hepatitis by taking advantage of WSX-1 knockout mice. WSX-1-deficient mice were more susceptible to Con A treatment than wild-type mice, showing serum alanine aminotransferase elevation and massive necrosis in the liver. Although the development of NKT cells appeared normal in WSX-1 knockout mice, purified NKT cells from the knockout mice produced more IFN-γ and IL-4 than those from wild-type mice in response to stimulation with Con A both in vitro and in vivo. In addition, hyperproduction of proinflammatory cytokines, including IL-1, IL-6, and TNF-α, was observed in the knockout mice after Con A administration. These data revealed a novel role for WSX-1 as an inhibitory regulator of cytokine production and inflammation in Con A-induced hepatitis.

AB - Administration of Con A induces liver injury that is considered to be an experimental model for human autoimmune or viral hepatitis, where immunopathology plays roles mediated by activated lymphocytes, especially NK1.1+ CD3+ NKT cells, and inflammatory cytokines, including IFN-γ and IL-4. In the present study we investigated the role of WSX-1, a component of IL-27R, in Con A-induced hepatitis by taking advantage of WSX-1 knockout mice. WSX-1-deficient mice were more susceptible to Con A treatment than wild-type mice, showing serum alanine aminotransferase elevation and massive necrosis in the liver. Although the development of NKT cells appeared normal in WSX-1 knockout mice, purified NKT cells from the knockout mice produced more IFN-γ and IL-4 than those from wild-type mice in response to stimulation with Con A both in vitro and in vivo. In addition, hyperproduction of proinflammatory cytokines, including IL-1, IL-6, and TNF-α, was observed in the knockout mice after Con A administration. These data revealed a novel role for WSX-1 as an inhibitory regulator of cytokine production and inflammation in Con A-induced hepatitis.

UR - http://www.scopus.com/inward/record.url?scp=1542409969&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1542409969&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.172.6.3590

DO - 10.4049/jimmunol.172.6.3590

M3 - Article

C2 - 15004160

AN - SCOPUS:1542409969

VL - 172

SP - 3590

EP - 3596

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 6

ER -