Identification of T-Cell specific signature miRNAs and target pathways in Psoriasis

Abstract

Psoriasis is a chronic skin disease characterized by keratinocyte hyperproliferation, involving T cells as the major players in the manifestation of lesional and systemic inflammation. With the extensive exploration of keratinocyte dysfunctionality, T cell centric deregulation has gained much focus with limited molecular understanding in the context of disease etiology. miRNAs, the molecular switches known to drive disease manifestation via altering keratinocyte biology, have not been much studied in the context of T cell alterations. This study aims to explore T cell-associated miRNAs and their target signaling networks to understand their role in modulating psoriasis specific T cell changes. miRNAs with altered expression in psoriatic T cells were identified through a comprehensive analysis of the available literature and datasets. The relevant miRNAs were used for prediction and enrichment of cognate targets and mapping of associated pathways involved in different modalities of T cell functionality. The study identified 14 miRNAs dysregulated in psoriatic T cells along with 256 downstream targets involved in 15 distinct T cell associated signaling pathways. 5/14 miRNAs identified were further validated with a significant increase in their expression in enriched CD3+T cells from blood of psoriatic patients versus healthy subjects. The psoriatic T cell specific miRNA driven signaling cascades identified were modelled to propose yet unexplored molecular basis of dysregulated T cell activation, proliferation, survival, and subset differentiation associated with the disease. The new findings delineate candidate miRNA target signaling components that need to be validated in T cell disease etiology. Importantly, the key miRNAs/targets can be employed towards psoriasis-specific diagnostics and therapeutic interventions.