Oral Presentation The 13th International Congress of the Immunology of Diabetes Society 2013

MicroRNA expression profiling reveals regulatory T cell defects mediated by polycomb repressive complex 2 in human autoimmune disease (#208)

Yuxia Zhang 1 , Zhi-Ping Feng 1 , Ajithkumar Vasanthakumar 1 , Sarah Kinkel 1 , Gaetano Naselli 1 , Fiona Bell 1 , James Wettenhall 2 , Marnie Blewitt 1 , Axel Kallies 1 , Terry Speed 1 , Mark Chong 3 , Leonard Harrison 1
  1. Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
  2. Characterisation Virtual Laboratory, Monash university, Clayton, Vic, Australia
  3. St Vincent’s Institute of Medical Research, Fitzroy, Vic, Australia

MicroRNAs (miRNAs) are important to maintain immune tolerance. To explore their pathogenic involvement in human autoimmune disease, we performed expression profiling of T cell subsets from healthy individuals and those at high-risk of type 1 diabetes (pre-T1D). Differentially expressed miRNAs were detected in each T cell subsets compared to naïve CD4+ T cells and between healthy and pre-T1D individuals, for example increased expression of miR-26a in activated natural regulatory T cells was associated with a reduction in the blood of EZH2 mRNA, which encodes the catalytic subunit of the polycomb repressive complex 2, in pre-T1D individuals. EZH2 was shown to be required for nTreg survival and for regulating the IL-2 receptor alpha chain (CD25) expression. Our findings suggest that alterations in the expression of specific miRNAs may contribute to impaired Treg function in autoimmune disease-prone individuals.