Determination of T-cell clonality and expression profiles of Toll-like receptors signaling pathway genes and related miRNAs in patients with mycosis fungoides

Abstract

Cutaneous T-cell lymphomas (CTCL) encompass a group of diseases characterized by the presence of malignant clonal CD4+ T lymphocytes in the skin. Mycosis fungoides (MF) is the most prevalent form of CTCL, accounting for approximately 60 % of cutaneous T-cell lymphomas and 50 % of all primary cutaneous lymphomas. Despite ongoing research, the precise pathogenesis of MF remains incompletely understood. Toll-like receptors (TLRs) have the ability to specifically recognize ligands, subsequently induce the expression of diverse genes and activate innate immunity within the cell. Furthermore, miRNAs play a crucial role in regulating various aspects of immune cell function. The aim of our study was to explore the potential roles of TLRs and the genes implicated in their signal transduction, along with the expression status of miRNAs in the mechanisms underlying MF. Additionally, we assessed the clonal status and compared it with clinicopathological data using a T-cell clonality assay. To determine the expression status of TLR pathway genes and miRNAs, we conducted RT-PCR analysis on 52 MF samples and 50 control paraffin block materials. Pathway analysis were conducted using the KEGG database. T-cell receptor (TCR) gamma clonality changes were evaluated. Results from the study revealed increased expressions of TLR-1,-4,-8, IRF7, TRAF3, MEK1, MEK2, Elk1, NFkB, hsa-miR-21-5p, and hsa-miR-155-5p, as well as decreased expressions of hsa-miR-130a-3p, hsa-miR-210-3p, and hsa-let-7e-5p in the MF group. TCR gamma clonal change analysis demonstrated that 55.5 % of the analysed DNAs exhibited monoclonal and biallelic patterns, while 45.5 % displayed polyclonality. These findings collectively suggest the potential influ-ence and therapeutic possibilities of the TLR signalling pathway in the molecular pathogenesis of MF.