Global miRNA expression in Treg cells from patients with pulmonary sarcoidosis indicates for targeting of MAPK and FOXO signaling pathways

Sarcoidosis is a multisystem granulomatous disorder predominantly involving the lungs. The disequilibrium between effector and regulatory lymphocytes (Treg cells) in sarcoidosis has been suggested. MicroRNAs (miRNAs) are small non-coding molecules necessary for proper T cell functioning. Certain miRNAs can lead to polarization of the inflammatory response via IL-2 and IFN-g signaling pathways, implicated in sarcoidosis. In the current study, increase in the plasma levels of IFN-g induced protein 10, MIG, IL-12, IL-2R and VEGF was found in patients with pulmonary sarcoidosis (PS). These results point at persistence of the Th1 immune response with putative defective Treg functions. Therefore, the global miRNA expression of Treg (CD4+/CD25+) subpopulation, from peripheral blood (PB) and bronchoalveolar lavage (BAL) of PS patients, was assessed. As a control Treg cells from PB of healthy individuals (HI) were used. In the array 743 miRNAs were tested, but only 139 miRNA were found to be expressed in Tregs. Among them 15 were significantly different from the Treg cells of HI. Most of those miRNAs were up-regulated in BAL Treg cells and only two of them were down-regulated (miR-130b and miR-150). According to DIANA miR-Path the miRNAs differentially expressed (DE) in PS Treg cells target genes from MAPK signaling pathway. Interestingly the same DE-miRNAs also target genes in FOXO signaling pathway. Several DE-miRNAs (miR-223, -155 and -132) were predicted to target FOXO directly, suggesting impairment in PS Treg cell function and differentiation. Acknowledgments: Supported by OPUS grant No. 2012/07/B/NZ5/02506 (NCN) and KNOW grants.