[HTML][HTML] MiR-125a targets effector programs to stabilize Treg-mediated immune homeostasis

W Pan, S Zhu, D Dai, Z Liu, D Li, B Li, N Gagliani… - Nature …, 2015 - nature.com
Nature communications, 2015nature.com
Although different autoimmune diseases show discrete clinical features, there are common
molecular pathways intimately involved. Here we show that miR-125a is downregulated in
peripheral CD4+ T cells of human autoimmune diseases including systemic lupus
erythematosus and Crohn's disease, and relevant autoimmune mouse models. miR-125a
stabilizes both the commitment and immunoregulatory capacity of Treg cells. In miR-125a-
deficient mice, the balance appears to shift from immune suppression to inflammation, and …
Abstract
Although different autoimmune diseases show discrete clinical features, there are common molecular pathways intimately involved. Here we show that miR-125a is downregulated in peripheral CD4+ T cells of human autoimmune diseases including systemic lupus erythematosus and Crohn’s disease, and relevant autoimmune mouse models. miR-125a stabilizes both the commitment and immunoregulatory capacity of Treg cells. In miR-125a-deficient mice, the balance appears to shift from immune suppression to inflammation, and results in more severe pathogenesis of colitis and experimental autoimmune encephalomyelitis (EAE). The genome-wide target analysis reveals that miR-125a suppresses several effector T-cell factors including Stat3, Ifng and Il13. Using a chemically synthesized miR-125a analogue, we show potential to re-programme the immune homeostasis in EAE models. These findings point to miR-125a as a critical factor that controls autoimmune diseases by stabilizing Treg-mediated immune homeostasis.
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