Journal
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Volume 179, Issue 11, Pages 992-998Publisher
AMER THORACIC SOC
DOI: 10.1164/rccm.200806-992OC
Keywords
allergy; Th2 cytokine; signal transducer and activator of transcription-6; repressor molecule
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Funding
- Medical Research Council [MC_U105178805] Funding Source: Medline
- Medical Research Council [MC_U105178805] Funding Source: researchfish
- MRC [MC_U105178805] Funding Source: UKRI
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Rationale: Th2 cytokines play an important role in allergic diseases. These cytokines activate signal transduction pathways, including Janus kinase/signal transducer and activator of transcription (STAT) signaling. Although the suppressor of cytokine signaling (SOCS) family protein, a negative regulator of the Janus kinase/STAT signaling pathway, contributes to helper T cell differentiation during immune responses, the role of SOCS proteins within the structural cells of a target organ has not been clarified in allergy. Objectives: To study the local function of SOCS in the development of asthma. Methods: We used mouse models of IL-13- and ovalbumin (OVA)induced allergic airway disease. Airway smooth muscle cells were cultured from patients with asthma. Measurements and Main Results: The administration of IL-13 induced not only airway responses but also SOCS1 expression at the local inflammatory site. The up-regulated SOCS1 markedly suppressed IL-13-dependent STAT6 activation and eotaxin expression and subsequently down-regulated IL-13-induced airway inflammatory responses. The inactivation of SOCS1 induced airway hyperresponsiveness after IL-13 treatment even in hyporesponsive CS7BL/6 background mice. In an OVA-induced model of allergic airway disease, allergen exposure up-regulated local SOCS1 expression, and the induction of SOCS1 in the airways attenuated allergen-induced airway responses. Inactivation of IL-13 inhibited SOCS1 induction in a model of allergic airway disease. Interestingly, airway smooth muscle cells from individuals with asthma had impaired upregulation of SOCS1 after IL-13 stimulation. Conclusions: SOCS1 induction by IL-13 in airway structural cells is critical to negatively control allergic airway disease.
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