microRNA management of NK‐cell developmental and functional programs

Abstract

Summary NK cells are innate lymphoid cells that are critical for host defense against infection, and mediate anti-tumor responses. MicroRNAs (miRNAs) are a large family of small non-coding RNAs that target the 3′UTR of mRNAs, thereby attenuating protein translation. The expression of miRNAs within human peripheral blood and mouse splenic NK cells has been cataloged, with the majority of the miRNA sequence pool represented in the top 60 most abundantly expressed miRNAs. Global miRNA deficiency within NK cells has confirmed their critical role in NK cell biology, including defects in NK cell development and altered functionality. Studies using gain- and loss-of-function of individual miRNAs in NK cells have demonstrated the role of specific miRNAs in regulating NK cell development, maturation, and activation. miRNAs also regulate fundamental NK cell processes including cytokine production, cytotoxicity, and proliferation. This review provides an update on the intrinsic miRNA regulation of NK cells, including miRNA expression profiles, as well as their impact on NK cell biology. Additional profiling is needed to better understand miRNA expression within NK cell developmental intermediates, subsets, tissues, and in the setting of disease. Furthermore, key open questions in the field as well as technical challenges in the study of miRNAs in NK cells are highlighted.

HHV-6A in vitro infection of thyrocytes and T cells alters the expression of miRNA associated to autoimmune thyroiditis

“…In particular, miR-155 is a pleiotropic modulator of innate and adaptive immunity [15–17], and might promote autoimmune inflammation [18]. Beside its role as tumor-suppressor [19], miR-16 was recently shown to affect NK function by repressing IFNγ expression [20], and to promote M1 pro-inflammatory type macrophage polarization, affecting T cell activation [21]. No data are instead available on miR-1238 potential functions in immunity, as it was so far recognized only as a tumor-suppressor factor [22].…”

MicroRNA-29b mediates altered innate immune development in acute leukemia

“…Indeed, mice that are genetically altered to inhibit expression of both TBET and EOMES lack mature NK cells (22). Recently, microRNAs (miRs) have also emerged as important regulators of immune cell development and function (23)(24)(25)(26), and the modulation of TBET and EOMES has been linked to miR-29b in T cell studies (23,27). To date, the importance of miR regulation of NK cell development in the setting of cancer has not been evaluated.…”

miRNAs as new molecular insights into inflammatory bowel disease: Crucial regulators in autoimmunity and inflammation

“…Recent advances have demonstrated that miRNAs are crucial in NK cell biology [50] . For instance, miR150 and miR181 regulate NK cell development [51,52] .…”