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STAT6 deficiency in a mouse model of allergen‐induced airways inflammation abolishes eosinophilia but induces infiltration of CD8 + T cells
Author(s) -
Seiko Miyata,
Tomohiro Matsuyama,
Taku Kodama,
Yasuhiro Nishioka,
Kozo Kuribayashi,
Kiyoshi Takeda,
Shizuo Akira,
Minoru Sugita
Publication year - 1999
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1046/j.1365-2222.1999.00405.x
Subject(s) - stat6 , immunoglobulin e , eosinophilia , ovalbumin , immunology , interleukin 4 , cd8 , biology , inflammation , cytokine , cytotoxic t cell , allergic inflammation , t cell , interleukin 13 , immune system , antibody , biochemistry , in vitro
Background The TH2‐type cytokines have been reported to contribute to the asthmatic response. STAT6 has an essential role in IL‐4 signalling and in production of TH2 cytokines from T cells and is involved in IgE and IgG1 responses after nematode infections, indicating that STAT6 has an important role in allergic diseases. Objective In this study we investigated the effects of STAT6 deficiency on allergen‐induced airways inflammation in mice. Methods Both ovalbumin (OVA)‐sensitized STAT6 deficient (STAT6 −/−) mice and wild‐type C57BL/6 mice were challenged with aerosolized OVA. Changes in inflammatory cell infiltration and cytokine levels in lung tissue as well as serum immunoglobulin levels were analysed in OVA‐challenged STAT6 −/− and wild‐type mice. Results The eosinophilia and lung damage normally resulting from aeroallergen challenge were not seen in STAT6 −/− mice. Expression of TH2 cytokines (IL‐4 and IL‐5) in the lung tissue as well as IgE and IgG1 responses after OVA challenge were profoundly reduced in STAT6 −/− mice, whereas expression of IFNγ was the same in STAT6 −/− mice and wild‐type mice after OVA challenge. Immunocytochemical analysis of T cells showed the infiltration of CD4 + T cells but not CD8 + T cells increased into the lung of wild‐type mice after OVA challenge. However, the OVA‐exposed STAT6 −/− mice demonstrated the infiltration of both CD4 + T cells and CD8 + T cells with a significant increase in percentage and total number of CD8 + T cells compared with OVA‐exposed wild‐type mice. Conclusion These results indicate that factors which signal through STAT6 are important regulators of eosinophilia of allergic airway inflammation, regulating TH2‐type cytokine production both in CD4 + T cells and CD8 + T cells.