TY - JOUR
T1 - miR-146a controls the resolution of T cell responses in mice
AU - Yang, Lili
AU - Boldin, Mark P.
AU - Yu, Yang
AU - Liu, Claret Siyuan
AU - Ea, Chee Kwee
AU - Ramakrishnan, Parameswaran
AU - Taganov, Konstantin D.
AU - Zhao, Jimmy L.
AU - Baltimore, David
PY - 2012/8
Y1 - 2012/8
N2 - 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.
AB - 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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U2 - 10.1084/jem.20112218
DO - 10.1084/jem.20112218
M3 - Article
C2 - 22891274
AN - SCOPUS:84866354593
SN - 0022-1007
VL - 209
SP - 1655
EP - 1670
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 9
ER -