STAT6 deficiency in a mouse model of allergen-induced airways inflammationabolishes eosinophilia but induces infiltration of CD8(+) T cells

Background The TH2-type cytokines have been reported to contribute to the a sthmatic response. STAT6 has an essential role in IL-4 signalling and in pr oduction of TH2 cytokines from T cells and is involved in IgE and IgG1 resp onses after nematode infections, indicating that STAT6 has an important rol e 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 a nd wild-type C57BL/6 mice were challenged with aerosolized OVA. Changes in inflammatory cell infiltration and cytokine levels in lung tissue as well a s serum immunoglobulin levels were analysed in OVA-challenged STAT6(-/-) an d wild-type mice. Results The eosinophilia and lung damage normally resulting from aeroallerg en 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 expressio n of IFN gamma was the same in STAT6(-/-) mice and wildtype mice after OVA challenge. Immunocytochemical analysis of T cells showed the infiltration o f CD4(+) T cells but not CD8(+) T cells increased into the lung of wild-typ e mice after OVA challenge. However, the OVA-exposed STAT6(-/-) mice demons trated the infiltration of both CD4(+) T cells and CD8(+) T cells with a si gnificant increase in percentage and total number of CD8(+) T cells compare d with OVA-exposed wild-type mice. Conclusion These results indicate that factors which signal through STAT6 a re important regulators of eosinophilia of allergic airway inflammation, re gulating TH2-type cytokine production both in CD4(+) T cells and CD8(+) T c ells.