RNASeq Analysis of Gene Expression in Naïve and Regulatory CD4+ T cells from Wild Type and YAP-deficient mice

Regulatory T cells (Tregs) are critical for maintaining self-tolerance and immune homeostasis, but their suppressive function can impede effective anti-tumor immune responses. Foxp3 is a transcription factor expressed in Tregs that is required for their function. The pathways and microenvironmental cues governing Foxp3 expression and Treg function are not completely understood. We found that Yes-associated protein (YAP), a co-activator of the Hippo pathway, is highly expressed in Tregs and bolsters Foxp3 expression and Treg function in vitro and in vivo. To assess how YAP influences patterns of gene expression in Tregs, naïve CD4+ T cells and Tregs were isolated from wild type mice and CD4+ T cell lineage-restricted YAP knockout mice (YAPflox/flox, CD4-Cre+). Gene expression by naïve CD4+ T cells and their resting and stimulated Treg counterparts was analyzed by RNASeq. Our findings reveal that YAP ablation undermines expression of multiple genes involved in the TGFß/SMAD signaling pathway in Tregs including Activin. These findings suggest that YAP potentiates activity along a pro-Treg signaling axis. Overall design: The gene expression patterns in naïve T cells and nTregs from Wild type and YAP cKO (YAP flox/flox,CD4-Cre+) mice were assessed and compared using RNASeq. Sequencing was performed using a Illumina Hiseq2000.

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Ni X, Tao J, Barbi J, Chen Q, Park BV, Li Z, Zhang N, Lebid A, Ramaswamy A, Wei P, Zheng Y, Zhang X, Wu X, Vignali P, Yang CP, Li H, Pardoll D, Lu L, Pan D, Pan F