T cell activation induces proteasomal degradation of Argonaute and rapid remodeling of the microRNA repertoire.

Activation induces extensive changes in the gene expression program of naive CD4(+) T cells, promoting their differentiation into helper T cells that coordinate immune responses. MicroRNAs (miRNAs) play a critical role in this process, and miRNA expression also changes dramatically during T cell differentiation. Quantitative analyses revealed that T cell activation induces global posttranscriptional miRNA down-regulation in vitro and in vivo.

An integrated nano-scale approach to profile miRNAs in limited clinical samples.

Profiling miRNA expression in cells that directly contribute to human disease pathogenesis is likely to aid the discovery of novel drug targets and biomarkers. However, tissue heterogeneity and the limited amount of human diseased tissue available for research purposes present fundamental difficulties that often constrain the scope and potential of such studies. We established a flow cytometry-based method for isolating pure populations of pathogenic T cells from bronchial biopsy samples of asthma patients, and optimized a high-throughput nano-scale qRT-PCR method capable of accurately measuring 96 miRNAs in as little as 100 cells.

Distinct roles of FOXA2 and FOXA3 in allergic airway disease and asthma.

Rationale: Increased production of mucus is a prominent feature of asthma. IL-13-driven mucous cell metaplasia is associated with decreased expression of the transcription factor FOXA2 and increased expression of the related transcription factor FOXA3 in animal and cell culture models.

Objectives: Establish how changes in FOXA2 and FOXA3 expression contribute to mucous metaplasia and determine whether FOXA2 and FOXA3 expression is altered in asthma.