| RAPID COMMUNICATION Regulation of Allergic Inflammation and Eosinophil Recruitment in Mice Lacking the Transcription Factor NFAT1: Role of Interleukin-4 (IL-4) and IL-5 (2008) | |||||||||||||
Abstract | |||||||||||||
| Transcription factors of the NFAT (nuclear factor of activated T cells) family regulate the expression of many genes encoding immunoregulatory cytokines and cell surface proteins during the immune response. The NFAT protein NFAT1 (NFATp) is expressed and functional in T cells, B cells, mast cells, and natural killer cells. Here we report a detailed analysis of the enhanced eosinophil responses of NFAT1deficient mice, observed in an in vivo model of allergic inflammation. In addition to the pleural eosinophilia described previously, NFAT1�/ � mice that have been sensitized with antigen display a significant increase, relative to wildtype mice, in the numbers of eosinophils in bone marrow and peripheral blood. After restimulation with antigen in vitro, antigen-responsive T cells from the draining lymph nodes of NFAT1�/ � mice show increased expression of mRNA encoding the Th2 cytokines interleukin-4 (IL-4), IL-5, ATOPY OR ALLERGIC disease is a complex familial disorder with multiple manifestations, including allergic asthma, rhinitis, conjunctivitis, and dermatitis. 1-3 Both eosinophils and mast cells have been implicated in the pathogenesis of allergic disease. The hallmark of these diseases is a pronounced increase in the level of serum IgE, reflecting the actions of the cytokines interleukin-4 (IL-4) and IL-13 to promote B-cell isotype switching to IgE. 4 IgE produced by allergen-reactive B cells binds to Fc � receptors present on the surface of mast cells and basophils; when challenged with allergen, these cells release vasoactive mediators that directly damage the surrounding tissue, as well as chemotactic factors and cytokines that promote leukocyte infiltration and exacerbate the inflammatory response. 2,4 Likewise, eosinophils accumulate at sites of allergic inflammation, produce leukotrienes and other inflammatory mediators, and contribute significantly to tissue damage at sites of allergic inflammation. 5 The magnitude of asthmatic responses is related to the number of eosinophils present in the lung, 6 and suppression of eosinophil accumulation at the site of inflammation impairs the development of airway hyperreactivity. | |||||||||||||
Publication details | |||||||||||||
| |||||||||||||