The Multifaceted Interface Between Cytokines and microRNAs: An Ancient Mechanism to Regulate the Good and the Bad of Inflammation

MicroRNAs (miRNAs) are evolutionary conserved small non-coding RNA molecules that affect gene expression by binding to target messenger RNAs and play a role in biological processes like cell growth, differentiation, and death. Different CD4+ T cell subsets such as Th1, Th2, Th17, and T regulatory cells, exert a distinct role in effector and regulatory-type immune responses. miRNAs have been shown to respond to dynamic micro-environmental cues and regulate multiple functions of T cell subsets including their development, survival and activation. Thus, miRNA functions contribute to immune homeostasis, on the one side, and to the control of immune tolerance, on the other. Among the most important proteins whose expression is targeted by miRNAs, there are the cytokines, that act as both key upstream signals and major functional outputs, and that, in turn, can affect miRNA level. Here, we analyze what is known about the regulatory circuit of miRNAs and cytokines in CD4+ T lymphocytes, and how this bidirectional system is dysregulated in conditions of pathological inflammation and autoimmunity. Furthermore, we describe how different T cell subsets release distinct fingerprints of miRNAs that modify the extracellular milieu and the inter-cellular communication between immune cells at the autocrine, paracrine, and endocrine level. In conclusion, a deeper knowledge of the interplay between miRNAs and cytokines in T cells may have pivotal implications for finding novel therapeutic strategies to target inflammation and autoimmune disorders.