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

C. Lee, Tatiana B Kolesnik, I. Caminschi, A. Chakravorty, Angus W Carter, W. S. Alexander, J. Jones, G. P. Anderson, S. E. Nicholson

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Background 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 in vitro 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. Objective To investigate the role of SOCS1 in regulating Th2-associated disease traits in a murine sub-chronic aeroallergen-driven asthma model. Methods Following sensitization and challenge with ovalbumin (OVA), bronchoalveolar lavage and serum were collected from mice lacking the Socs1 gene on an IFN-γ null background (Socs1-/-Ifnγ-/-). The composition of infiltrating cells in the lung, serum IgE and IgG1 levels and cytokine levels were analysed. Results Serum IgE levels and infiltrating eosinophils were considerably increased in the lungs of OVA-treated Socs1-/-Ifnγ -/- mice compared with Ifnγ-/- and C57BL/6 controls. Expression of the Th2 cytokines, IL-4, IL-5 and IL-13 was increased in CD4 + cells and lung tissue from OVA-treated Socs1 -/-Ifnγ-/- mice. IgE, IL-5 levels and infiltrating eosinophils were also elevated in saline-treated Socs1 -/-Ifnγ-/- 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 Socs1-/-Ifnγ-/- mice, suggesting that regulation by SOCS1 occurs primarily in haematopoietic cells and not in the airway epithelium. Conclusions Together these results indicate that SOCS1 is an important regulator of the Th2 response.

Original languageEnglish
Pages (from-to)897-907
Number of pages11
JournalClinical and Experimental Allergy
Issue number6
Publication statusPublished - Jun 2009
Externally publishedYes


  • Asthma
  • Bronchoalveolar lavage
  • Eosinophils
  • SOCS1
  • Th2-type cytokines

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