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

Lee, C; Kolesnik, TB; Caminschi, I; Chakravorty, A; Carter, W; Alexander, WS; Jones, J; Anderson, GP; Nicholson, SE

Author(s): Lee, C; Kolesnik, TB; Caminschi, I; Chakravorty, A; Carter, W; Alexander, WS; Jones, J; Anderson, GP; Nicholson, SE;
Details: Publication Year 2009-06,Volume 39,Issue #6,Page 897-907
Journal Title: CLINICAL AND EXPERIMENTAL ALLERGY
Publication Type: Journal Article
Abstract: 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. To investigate the role of SOCS1 in regulating Th2-associated disease traits in a murine sub-chronic aeroallergen-driven asthma model. Following sensitization and challenge with ovalbumin (OVA), bronchoalveolar lavage and serum were collected from mice lacking the Socs1 gene on an IFN-gamma null background (Socs1(-/-)Ifn gamma(-/-)). The composition of infiltrating cells in the lung, serum IgE and IgG1 levels and cytokine levels were analysed. Serum IgE levels and infiltrating eosinophils were considerably increased in the lungs of OVA-treated Socs1(-/-)Ifn gamma(-/-) mice compared with Ifn gamma(-/-) 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(-/-)Ifn gamma(-/-) mice. IgE, IL-5 levels and infiltrating eosinophils were also elevated in saline-treated Socs1(-/-)Ifn gamma(-/-) 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(-/-)Ifn gamma(-/-) mice, suggesting that regulation by SOCS1 occurs primarily in haematopoietic cells and not in the airway epithelium. Together these results indicate that SOCS1 is an important regulator of the Th2 response.
Publisher: WILEY-BLACKWELL PUBLISHING, INC
Keywords: INDUCED AIRWAY HYPERRESPONSIVENESS; DEFICIENT MICE; T-CELLS; ALLERGIC-ASTHMA; IFN-GAMMA; IN-VIVO; IL-4; HYPERREACTIVITY; MECHANISMS; RECEPTOR
Publisher's Version: https://doi.org/10.1111/j.1365-2222.2009.03217.x
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2009-06-01 12:00:00