Aberrant IL-4 production by SOCS3-over-expressing T cells during infection with Leishmania major exacerbates disease manifestations

Mako Nakaya, Shinjiro Hamano, Miyuri Kawasumi, Hiroki Yoshida, Akihiko Yoshimura, Takashi Kobayashi

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Suppressor of cytokine signaling (SOCS) 3 is a major negative feedback regulator of signal transducer and activator of transcription 3-activating cytokines. Studies using T-cell-specific SOCS3-deficient mice indicate that the absence of SOCS3 in T cells results in exacerbation of disease progression after infection by Leishmania major due to skewing of the Th3 cell phenotype accompanied by hyper-production of IL-10 and transforming growth factor β (TGF-β). Here we show that transgenic mice over-expressing the SOCS3 gene in T cells (Lck-SOCS3 Tg mice) are also susceptible to infection by L. major. Forced expression of SOCS3 in T cells did not affect the production of the anti-inflammatory cytokines IL-10 and TGF-β or that of the protective Th1 type cytokine IFN-γ, which is required for parasite clearance. CD41 T cells isolated from infected-Lck-SOCS3 Tg mice produced much higher levels of IL-4 when they were restimulated with L. major antigen in vitro. Exacerbation of disease progression in Lck-SOCS3 Tg mice was completely reversed by administration of a neutralizing antibody against IL-4. These data suggest that tight regulation of SOCS3 expression in Th cells is crucial for disease control during infection by L. major.

Original languageEnglish
Pages (from-to)195-202
Number of pages8
JournalInternational Immunology
Volume23
Issue number3
DOIs
Publication statusPublished - 2011

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Leishmania major
Interleukin-4
T-Lymphocytes
Cytokines
Infection
Interleukin-10
Disease Progression
STAT3 Transcription Factor
Transforming Growth Factors
Regulatory T-Lymphocytes
Infection Control
Neutralizing Antibodies
Transgenic Mice
Parasites
Anti-Inflammatory Agents
Phenotype
Antigens
Genes

Keywords

  • Cytokine
  • Regulatory T cell
  • T1
  • T2

ASJC Scopus subject areas

  • Immunology

Cite this

Aberrant IL-4 production by SOCS3-over-expressing T cells during infection with Leishmania major exacerbates disease manifestations. / Nakaya, Mako; Hamano, Shinjiro; Kawasumi, Miyuri; Yoshida, Hiroki; Yoshimura, Akihiko; Kobayashi, Takashi.

In: International Immunology, Vol. 23, No. 3, 2011, p. 195-202.

Research output: Contribution to journalArticle

Nakaya, Mako ; Hamano, Shinjiro ; Kawasumi, Miyuri ; Yoshida, Hiroki ; Yoshimura, Akihiko ; Kobayashi, Takashi. / Aberrant IL-4 production by SOCS3-over-expressing T cells during infection with Leishmania major exacerbates disease manifestations. In: International Immunology. 2011 ; Vol. 23, No. 3. pp. 195-202.
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