@article{e6c0587a0b2140428f3fbd366749554b,
title = "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 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.",
keywords = "Cytokine, Regulatory T cell",
author = "Mako Nakaya and Shinjiro Hamano and Miyuri Kawasumi and Hiroki Yoshida and Akihiko Yoshimura and Takashi Kobayashi",
note = "Funding Information: Special Grants-in-Aid for Scientific Research on Priority Areas (19041058 to T.K.), for Scientific Research on Innovative Areas (22117516 to T.K.), for Scientific Research (20590492 to T.K.), for Young Scientists (22790472 to M.N.) and Special Coordination Fund for Promoting Science and Technology Improvement of research environment for young researchers Carrier development program for young investigators in {\textquoteleft}{\textquoteleft}Cell and Metabolism Research{\textquoteright}{\textquoteright} from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO), the Nakatomi Foundation, the Takeda Science Foundation, The Kato Memorial Trust Foundation for Nanbyo Research, the Suzuken Memorial Foundation, the Japan Intractable Disease Research Foundation, the Naito Foundation, the Mochida Memorial Foundation for Medical and Pharmaceutical Research, Astellas Foundation for Research on Metabolic Disorders, the Yakult Bioscience Research Foundation, and the Princess Takamatsu Cancer Research Fund.",
year = "2011",
month = mar,
day = "1",
doi = "10.1093/intimm/dxq472",
language = "English",
volume = "23",
pages = "195--202",
journal = "International immunology",
issn = "0953-8178",
publisher = "Oxford University Press",
number = "3",
}