Regulation of immune responses and tolerance: the micro RNA perspective

Summary Much has been learned about the molecular and cellular components critical for the control of immune responses and tolerance. It remains a challenge, however, to control the immune response and tolerance at the system level without causing significant toxicity to normal tissues. Recent studies suggest that micro RNA (mi RNA ) genes, an abundant class of non‐coding RNA genes that produce characteristic approximately 22 nucleotides small RNA s, play important roles in immune cells. In this article, we discuss emerging knowledge regarding the functions of mi RNA genes in the immune system. We delve into the roles of mi RNA s in regulating signaling strength and threshold, homeostasis, and the dynamics of the immune response and tolerance during normal and pathogenic immunological conditions. We also present observations based on analyzes of miR‐181 family genes that indicate the potential functions of primary and/or precursor mi RNA s in target recognition and explore the impact of these findings on target identification. Finally, we illustrate that despite the subtle effects of mi RNA s on gene expression, mi RNA s have the potential to influence the outcomes of normal and pathogenic immune responses by controlling the quantitative and dynamic aspects of immune responses. Tuning mi RNA functions in immune cells, through gain‐ and loss‐of‐function approaches in mice, may reveal novel approach to restore immune equilibrium from pathogenic conditions, such as autoimmune disease and leukemia, without significant toxicity.