Suppressor of cytokine signalling 1 (SOCS1) is a physiological regulator of the asthma response

<jats:title>Summary</jats:title><jats:p><jats:bold>Background </jats:bold> The molecular determinants of the severity and persistence of allergic asthma remain poorly understood. Suppressor of cytokine signalling 1 (SOCS1) is a negative regulator of IL‐4‐dependent pathways <jats:italic>in vitro</jats:italic> and might therefore control T‐helper type 2 (Th2) immunity associated traits, such as IgE levels, mucin production, IL‐5 and IL‐13 induction, and eosinophilic mucosal inflammation, which are implicated in allergic asthma.</jats:p><jats:p><jats:bold>Objective </jats:bold> To investigate the role of SOCS1 in regulating Th2‐associated disease traits in a murine sub‐chronic aeroallergen‐driven asthma model.</jats:p><jats:p><jats:bold>Methods </jats:bold> Following sensitization and challenge with ovalbumin (OVA), bronchoalveolar lavage and serum were collected from mice lacking the <jats:italic>Socs1</jats:italic> gene on an IFN‐γ null background (<jats:italic>Socs1</jats:italic><jats:sup>−/−</jats:sup><jats:italic>Ifn</jats:italic>γ<jats:sup>−/−</jats:sup>). The composition of infiltrating cells in the lung, serum IgE and IgG1 levels and cytokine levels were analysed.</jats:p><jats:p><jats:bold>Results </jats:bold> Serum IgE levels and infiltrating eosinophils were considerably increased in the lungs of OVA‐treated <jats:italic>Socs1</jats:italic><jats:sup>−/−</jats:sup><jats:italic>Ifn</jats:italic>γ<jats:sup>−/−</jats:sup> mice compared with <jats:italic>Ifn</jats:italic>γ<jats:sup>−/−</jats:sup> and C57BL/6 controls. Expression of the Th2 cytokines, IL‐4, IL‐5 and IL‐13 was increased in CD4<jats:sup>+</jats:sup> cells and lung tissue from OVA‐treated <jats:italic>Socs1</jats:italic><jats:sup>−/−</jats:sup><jats:italic>Ifn</jats:italic>γ<jats:sup>−/−</jats:sup> mice. IgE, IL‐5 levels and infiltrating eosinophils were also elevated in saline‐treated <jats:italic>Socs1</jats:italic><jats:sup>−/−</jats:sup><jats:italic>Ifn</jats:italic>γ<jats:sup>−/−</jats:sup> mice, suggesting that in the absence of SOCS1, mice are already biased towards a Th2 response. It is at present unclear whether the elevated cytokine levels are sufficient to result in the exacerbated Th2 response to OVA challenge or whether enhanced intra‐cellular signalling also contributes. Surprisingly, of the various IL‐4/IL‐13 responsive genes tested, only Arginase I appeared to be modestly up‐regulated in the lungs of OVA‐treated <jats:italic>Socs1</jats:italic><jats:sup>−/−</jats:sup><jats:italic>Ifn</jats:italic>γ<jats:sup>−/−</jats:sup> mice, suggesting that regulation by SOCS1 occurs primarily in haematopoietic cells and not in the airway epithelium.</jats:p><jats:p><jats:bold>Conclusions </jats:bold> Together these results indicate that SOCS1 is an important regulator of the Th2 response.</jats:p>