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

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 T(h)3 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 T(h)1 type cytokine IFN-γ, which is required for parasite clearance. CD4(+) T cells isolated from infected-Lck-SOCS3 Tg mice produced much higher levels of IL-4 when they were re-stimulated 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 T(h) cells is crucial for disease control during infection by L. major.

• Authors: Mako Nakaya, Shinjiro Hamano, Miyuri Kawasumi, Hiroki Yoshida, Akihiko Yoshimura, Takashi Kobayashi
• Journal: International immunology (Int Immunol) Vol. 23 Issue 3 Pg. 195-202 (Mar 2011) ISSN: 1460-2377 [Electronic] England
• PMID: 21393635 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• SOCS3 protein, human
• Suppressor of Cytokine Signaling 3 Protein
• Suppressor of Cytokine Signaling Proteins
• Interleukin-4

Topics

• Animals
• Cytokines (immunology)
• Disease Progression
• Gene Expression
• Interleukin-4 (immunology)
• Leishmania major (physiology)
• Leishmaniasis, Cutaneous (immunology, physiopathology)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Signal Transduction
• Suppressor of Cytokine Signaling 3 Protein
• Suppressor of Cytokine Signaling Proteins (genetics, metabolism)
• T-Lymphocytes (immunology)
• T-Lymphocytes, Regulatory (immunology)
• Time Factors