Sourabh Tyagi

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.