Overexpression of suppressor of cytokine signalling-5 augments eosinophilic airway inflammation in mice
Article first published online: 20 APR 2007
Clinical & Experimental Allergy
Volume 37, Issue 5, pages 735–742, May 2007
How to Cite
Ohshima, M., Yokoyama, A., Ohnishi, H., Hamada, H., Kohno, N., Higaki, J. and Naka, T. (2007), Overexpression of suppressor of cytokine signalling-5 augments eosinophilic airway inflammation in mice. Clinical & Experimental Allergy, 37: 735–742. doi: 10.1111/j.1365-2222.2007.02707.x
- Issue published online: 20 APR 2007
- Article first published online: 20 APR 2007
- Submitted 28 December 2006; revised 20 January 2007; accepted 23 February 2007
- CD4+ T cells;
- epidermal growth factor;
Background Enhanced expression of the suppressor of cytokine signalling (SOCS)-5 might be of therapeutic benefit for T-helper type 2 (Th2) dominant diseases, as its expression is reported to result in a reduction of Th2 differentiation in vitro due to the inhibition of IL-4 signalling.
Objective To investigate the regulatory role of SOCS-5 in vivo, we explored the phenotype of an experimental asthma model developed in SOCS-5 transgenic (Tg) mice.
Methods The SOCS-5 Tg mice or wild-type (WT) mice were sensitized and repeatedly challenged with ovalbumin (OVA). We examined bronchoalveolar lavage fluid (BALF), lung specimens, and airway hyperresponsiveness (AHR) to methacholine.
Results The production of IFN-γ by CD4+ T cells from unprimed SOCS-5 Tg mice was significantly increased in comparison with unprimed wild-type mice, indicating that SOCS-5 Tg mice have a Th1-polarizing condition under natural conditions. However, in an asthma model, significantly more eosinophils in the airways and higher levels of IL-5 and IL-13 in BALF were observed in the SOCS-5 Tg than the wild-type mice. AHR in the asthma model of SOCS-5 Tg was also more enhanced than that of wild-type mice. OVA-stimulated CD4+ T cells from the primed SOCS-5 Tg mice produced significantly more IL-5 and IL-13 than CD4+ T cells from wild-type mice.
Conclusion Our results demonstrate that the overexpression of SOCS-5 does not inhibit Th2 response, but rather augments the phenotype of the asthma model in vivo. This finding throws into question the therapeutic utility of using enhancement of SOCS-5 expression for Th2-dominant disease.