miR-181a Is an Intrinsic Modulator of T Cell Sensitivity and Selection

T cell sensitivity to antigen is intrinsically regulated during maturation to ensure proper development of immunity and tolerance, but how this is accomplished remains elusive. Here we show that increasing miR-181a expression in mature T cells augments the sensitivity to peptide antigens, while inhi...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Cell 2007-04, Vol.129 (1), p.147-161
Hauptverfasser: Li, Qi-Jing, Chau, Jacqueline, Ebert, Peter J.R., Sylvester, Giselle, Min, Hyeyoung, Liu, Gwen, Braich, Ravi, Manoharan, Muthiah, Soutschek, Juergen, Skare, Petra, Klein, Lawrence O., Davis, Mark M., Chen, Chang-Zheng
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:T cell sensitivity to antigen is intrinsically regulated during maturation to ensure proper development of immunity and tolerance, but how this is accomplished remains elusive. Here we show that increasing miR-181a expression in mature T cells augments the sensitivity to peptide antigens, while inhibiting miR-181a expression in the immature T cells reduces sensitivity and impairs both positive and negative selection. Moreover, quantitative regulation of T cell sensitivity by miR-181a enables mature T cells to recognize antagonists—the inhibitory peptide antigens—as agonists. These effects are in part achieved by the downregulation of multiple phosphatases, which leads to elevated steady-state levels of phosphorylated intermediates and a reduction of the T cell receptor signaling threshold. Importantly, higher miR-181a expression correlates with greater T cell sensitivity in immature T cells, suggesting that miR-181a acts as an intrinsic antigen sensitivity “rheostat” during T cell development.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2007.03.008