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The immune system has evolved to mount effective responses to numerous and enormously diverse microbial pathogens. Specifically, T cells are able to respond to different environmental cues and differentiate into distinct helper T (Th) subsets through acquiring “master transcription factors and secreting distinctive cytokines for proper host defense. However, immune activation caused by immune responses against self and foreign antigens need to be tightly controlled to prevent overt inflammation and tissue damage. To this end, a specific subset of T cells, so-called regulatory T (Treg) cells is absolutely necessary for the negative regulation of T cell-mediated immune responses. Several studies show the loss of Treg-mediate regulation can lead to the lost of peripheral tolerance, and the onset of different autoimmune diseases. Additionally, discovery of microRNAs (miRNAs) have been demonstrated to mediate immune regulation through post-transcriptional gene regulation. Direct binding of miRNA at the 3’ untranslated region located on the mRNA targets leads to mRNA degradation. Of interest, miR-23∼27∼24 cluster contains a unique expression profile with differentially low expression in conventional T (Tconv) cells while maintaining high levels in Treg cells. We hypothesized low expression of this miRNA family is necessary for proper effector T cell function at both physiological and pathological settings. We show that the miR-23∼27∼24 clusters are capable in regulating T cell biology in a collaborative manner, particularly Th2 immunity. Previously, elevated miR-27 expression in T cells isolated from multiple sclerosis patients has been suggested to facilitate disease progression through inhibiting Th2 immunity and promoting Th1 responses. We demonstrate that while mice with T cell-specific overexpression of miR-27 harbor dysregulated Th1 responses and develop autoimmune pathology these disease phenotypes are not driven by miR-27 in effector T cells in a cell-autonomous m

The immune system has evolved to mount effective responses to numerous and enormously diverse microbial pathogens. Specifically, T cells are able to respond to different environmental cues and differentiate into distinct helper T (Th) subsets through acquiring “master transcription factors and secreting distinctive cytokines for proper host defense. However, immune activation caused by immune responses against self and foreign antigens need to be tightly controlled to prevent overt inflammation and tissue damage. To this end, a specific subset of T cells, so-called regulatory T (Treg) cells is absolutely necessary for the negative regulation of T cell-mediated immune responses. Several studies show the loss of Treg-mediate regulation can lead to the lost of peripheral tolerance, and the onset of different autoimmune diseases. Additionally, discovery of microRNAs (miRNAs) have been demonstrated to mediate immune regulation through post-transcriptional gene regulation. Direct binding of miRNA at the 3’ untranslated region located on the mRNA targets leads to mRNA degradation. Of interest, miR-23∼27∼24 cluster contains a unique expression profile with differentially low expression in conventional T (Tconv) cells while maintaining high levels in Treg cells. We hypothesized low expression of this miRNA family is necessary for proper effector T cell function at both physiological and pathological settings. We show that the miR-23∼27∼24 clusters are capable in regulating T cell biology in a collaborative manner, particularly Th2 immunity. Previously, elevated miR-27 expression in T cells isolated from multiple sclerosis patients has been suggested to facilitate disease progression through inhibiting Th2 immunity and promoting Th1 responses. We demonstrate that while mice with T cell-specific overexpression of miR-27 harbor dysregulated Th1 responses and develop autoimmune pathology these disease phenotypes are not driven by miR-27 in effector T cells in a cell-autonomous m