Eosinophil Development, Regulation of Eosinophil-Specific Genes, and Role of Eosinophils in the Pathogenesis of Asthma.
- Author:
Tae Gi UHM
1
;
Byung Soo KIM
;
Il Yup CHUNG
Author Information
- Publication Type:Review
- Keywords: Asthma; CCR3; eosinophils; eotaxin; GATA-1; IL-5
- MeSH: Aluminum Hydroxide; Animals; Asthma; Biology; Bone Marrow; Carbonates; Eosinophil Major Basic Protein; Eosinophils; Exons; Humans; Immunity, Innate; Interleukin-5; Interleukins; Introns; Lung; Mice; Multipotent Stem Cells; Receptors, CCR3; Stem Cells; Transcription Factors
- From:Allergy, Asthma & Immunology Research 2012;4(2):68-79
- CountryRepublic of Korea
- Language:English
- Abstract: Eosinophils arise from hematopoietic CD34+ stem cells in the bone marrow. They acquire IL-5Ralpha on their surface at a very early stage during eosinophilopoiesis, and differentiate under the strong influence of interleukin (IL)-5. They then exit to the bloodstream, and enter the lung upon exposure to airway inflammatory signals, including eotaxins. In inflamed tissues, eosinophils act as key mediators of terminal effector functions and innate immunity and in linking to adaptive immune responses. Transcription factors GATA-1, CCAAT/enhancer-binding protein, and PU.1 play instructive roles in eosinophil specification from multipotent stem cells through a network of cooperative and antagonistic interactions. Not surprisingly, the interplay of these transcription factors is instrumental in forming the regulatory circuit of expression of eosinophil-specific genes, encoding eosinophil major basic protein and neurotoxin, CC chemokine receptor 3 eotaxin receptor, and IL-5 receptor alpha. Interestingly, a common feature is that the critical cis-acting elements for these transcription factors are clustered in exon 1 and intron 1 of these genes rather than their promoters. Elucidation of the mechanism of eosinophil development and activation may lead to selective elimination of eosinophils in animals and human subjects. Furthermore, availability of a range of genetically modified mice lacking or overproducing eosinophil-specific genes will facilitate evaluation of the roles of eosinophils in the pathogenesis of asthma. This review summarizes eosinophil biology, focusing on development and regulation of eosinophil-specific genes, with a heavy emphasis on the causative link between eosinophils and pathological development of asthma using genetically modified mice as models of asthma.
