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Transcriptional Regulators in Allergy and Asthma

The early and late phase asthmatic responses are initiated by the recognition and processing of allergens by dendritic cells which drive naïve T cells to differentiate into T helper type 2 cells (Th2). Th2 lineage commitment is established by STAT6-dependent expression of GATA-3 which induces the expression of Th2 cytokines, including IL-3, IL-4, IL-5, IL-9, IL-13, and GM-CSF. Together these cytokines direct the inflammatory response to allergens.

The STAT family of transcription factors are characterized structurally by the presence of the Src homology 2 (SH2) domain, and a C-terminal tyrosine phosphorylation site. Upon ligand binding, they are recruited to the activated receptor, via their SH2 domains, to receptor-associated tyrosine kinases of the Janus kinase family (JAK). Once phosphorylated by JAK, STATS are free to hetero- or homo-dimerize, and translocate to the nucleus where they bind DNA to regulate gene transcription. GATA proteins are transcriptional coactivators with two GATA-type zinc fingers. GATAs bind to the consensus DNA sequence (A/T) GATA (A/G) to control diverse tissue-specific programs of gene expression and morphogenesis. R&D Systems also offers products for FoxP3, HIF (hypoxia-inducible transcription factor) and NFkB, additional transcription factors implicated in the signaling cascades that underlie the immune response to inhaled pathogens.