Mir-4443, a Possible Participant in Mast Cell Activation By T Cell-Derived Microvesicles
Sunday, March 5, 2017: 1:45 PM
Room B314 (Georgia World Congress Center, Building B)
Yoseph A Mekori,

The mechanism by which mast cells are activated in T cell-mediated inflammatory processes remains elusive.  In this regard, we have recently shown that mast cells can be activated by microvesicles (MVs) derived from activated T cells (mvT*) to degranulate and release several cytokines. The aim of this study was to analyze the possible effect of microRNAs delivered by MVs on mast cell activation. 


The high-throughput microRNA profiling was performed using NanoString technology platform and was validated by real time PCR. The biological role of mvT*- derived microRNA was verified by overexpression of these microRNAs in mast cells using mimic or inhibitory molecules and analyzing their predicted targets.


T cell-derived microvesicles were found to downregulate the tyrosine phosphatase PTPRJ expression, a known ERK inhibitor. Bioinformatics analysis revealed that miR-4443 is predicted to regulate the PTPRJ gene. Indeed, miR-4443 present in mvT*, was also found to be overexpressed in human mast cells stimulated with this MVs. Luciferase reporter assay indicated that 3'UTR of PTPRJ was the target of this miR. Transfection of mast cells with mimic or inhibitor of miR-4443 resulted in decreased or enhanced PTPRJ expression respectively. Furthermore, miR-4443 was found to regulate ERK-phosphorylation and IL-8 release in mast cells activated by mvT*. 


These results support a scenario by which T cell-derived MVs may act as intercellular carriers of functional miR 4443 that may exert heterotypic regulation of PTPRJ gene expression in mast cells leading to their activation in the context of T cell-mediated inflammatory processes.