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CD4+ helper T cells differentiate into distinct subtypes, Th1 and Th2 cells. Th2 cells are involved in the response to extracellular helminthe parasites and allergic responses and secrete a distinct set of cytokines including IL-4, IL-5 and IL-13. The development and differentiation of T cells is influenced by many factors, including transcription factors such as GATA-3, a transcription factor associated with induction of Th2 cells. Factors that increase cAMP levels in Th2 cells activate p38 kinase, which phosphorylates and activates GATA-3 independently of PKA. Cells expressing GATA-3 develop the profile of Th2 cells, secreting IL-4, IL-5 and IL-13. These cytokines are found in a gene cluster together and are regulated coordinately by GATA-3. Binding of GATA-3 in the regulatory regions of these genes alters chromatin structure, increasing accessibility to other transcription factors. Activation of the T cell receptor through interaction with antigen on antigen presenting cells activates NFAT and other transcription factors that cooperate with GATA-3 in inducing Th2 cell differentiation. Dominant negative GATA-3 can repress the secretion of these cytokines and block the airway inflammation that causes asthma. Blocking GATA-3 action such as through antisense treatment has been suggested as a therapeutic strategy to treat asthma. GATA-3 has also been implicated in developmental processes such as the development of the inner ear. |
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Glenn Croston, PhD. |
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Asnagli H, Murphy K (2001) The functional genomics experience (are you experienced?). Nature Immunology 2: pp 826-828.
Chen C, Zhang D, LaPorte J, Ray A (2000) Cyclic AMP Activates p38 Mitogen-Activated Protein Kinase in Th2 Cells: Phosphorylation of GATA-2 and Stimulation of Th2 Cytokine Gene Expression. J Immunology 165: pp 5597-5605.
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