MicroRNA Profiles of TH Cells (47.11)

• Published in: The Journal of immunology (1950) Vol. 182; no. 1_Supplement; pp. 47 - 47.11
• Main Authors: Batts, LaKeisha, Coarfa, Cristian, Creighton, Chad, Gunarante, Preethi, Corry, David
• Format: Journal Article
• Language: English
• Published: 01-04-2009
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.182.Supp.47.11

Abstract
Naïve CD4+ T cells differentiate into two classes of helper effector (TH) cells during exposure to antigen within peripheral lymphoid tissues. TH1 cells are generated in the presence of IL-12 and IFN-γ whereas TH2 cells result from the influence of IL-4 and IL-6. These cells orchestrate adaptive immune responses by regulating: T cell effector differentiation, macrophage activation, and antibody isotype switching. The mechanisms that control CD4+ T cell differentiation are not yet fully defined. These short transcripts regulate gene expression and are capable of defining and altering cell fate. The importance of miRNA function in T-helper cell differentiation and function has yet to be determined. Using Next Generation Sequencing, we have begun to dissect the smallRNAome of TH cells before and after differentiation. We found enhanced induction of miRNAs in TH1 cells (64% vs. 55% in naïve) relative to TH2 cells (45% vs. 55% in naïve) suggesting a role for miRNAs in TH cell differentiation. miRNAs mmu-let-7c and mmu-mir-181a, which have previously been shown to function in TH cell development and activation were increased in expression in TH1 cells. Expression of two additional miRNAs, mmu-mir-199a and mmu-mir-101a, were also enhanced in both TH1 and TH2 cells and based on their putative immune targets STAT6 and IL-4Rα, we propose that they critically regulate TH1 and TH2 cell differentiation. We further discovered novel miRNAs that putatively target GATA3 and several genes related to cell survival and apoptosis. Understanding how differentially expressed miRNAs function in TH cell differentiation will pave the way for novel and highly specific therapies for TH cell-mediated diseases.