An altered balance between pathogenic and regulatory pathways in autoimmunity has been hypothesized and at times demonstrated in peripheral blood of patients with type 1 diabetes. However, our knowledge in humans at the sites of the autoimmune attack (i.e., the pancreas) is scanty. Studies generated in our lab. demonstrate that FOXP3⁺ T regulatory (Treg) cells, identified based on their epigenetic imprinting, are present within the pancreatic lymph-nodes of patients with type 1 diabetes but they lack a suppressive activity towards both polyclonal and insulin-specific effector responses. We have found that there is an important discrepancy in Treg cells of T1D patients between their epigenetic imprinting, FOXP3 expression and regulatory function when these cells reside in the draining lymph nodes but not when they circulate in the blood.

Given the crucial role that microRNA (miRNA) genes have demonstrated in modulating immune responses, it is possible that dysregulation of miRNA-expression contributes to the pathogenesis of autoimmune diseases, type 1 diabetes included, as recently demonstrated in other autoimmune diseases (e.g. multiple sclerosis).

Objectives of our work are: (i) to characterize the miRNA expression profile in Treg cells residing in different tissues of the same donor (healthy and with type 1 diabetes), and (ii) to understand whether Treg cells residing in the lymph-nodes of T1D patients are post-transcriptionally regulated in a different way than those isolated from healthy donors. Results from this study may be instrumental for our comprehension of type 1 diabetes and for the development of novel therapeutics to target miRNAs to modulate immune responses.