miR-146a controls the resolution of T cell responses in mice

L Yang, MP Boldin, Y Yu, CS Liu, CK Ea… - Journal of Experimental …, 2012 - rupress.org
L Yang, MP Boldin, Y Yu, CS Liu, CK Ea, P Ramakrishnan, KD Taganov, JL Zhao
Journal of Experimental Medicine, 2012rupress.org
T cell responses in mammals must be tightly regulated to both provide effective immune
protection and avoid inflammation-induced pathology. NF-κB activation is a key signaling
event induced by T cell receptor (TCR) stimulation. Dysregulation of NF-κB is associated
with T cell–mediated inflammatory diseases and malignancies, highlighting the importance
of negative feedback control of TCR-induced NF-κB activity. In this study we show that in
mice, T cells lacking miR-146a are hyperactive in both acute antigenic responses and …
T cell responses in mammals must be tightly regulated to both provide effective immune protection and avoid inflammation-induced pathology. NF-κB activation is a key signaling event induced by T cell receptor (TCR) stimulation. Dysregulation of NF-κB is associated with T cell–mediated inflammatory diseases and malignancies, highlighting the importance of negative feedback control of TCR-induced NF-κB activity. In this study we show that in mice, T cells lacking miR-146a are hyperactive in both acute antigenic responses and chronic inflammatory autoimmune responses. TCR-driven NF-κB activation up-regulates the expression of miR-146a, which in turn down-regulates NF-κB activity, at least partly through repressing the NF-κB signaling transducers TRAF6 and IRAK1. Thus, our results identify miR-146a as an important new member of the negative feedback loop that controls TCR signaling to NF-κB. Our findings also add microRNA to the list of regulators that control the resolution of T cell responses.
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