title: miR-181a is an intrinsic modulator of T cell sensitivity and selection.
abstract: 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.
authors: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors: Qi-Jing
authors: QJ
authors: Li
authors: Jacqueline
authors: J
authors: Chau
authors: Peter J R
authors: PJ
authors: Ebert
authors: Giselle
authors: G
authors: Sylvester
authors: Hyeyoung
authors: H
authors: Min
authors: Gwen
authors: G
authors: Liu
authors: Ravi
authors: R
authors: Braich
authors: Muthiah
authors: M
authors: Manoharan
authors: Juergen
authors: J
authors: Soutschek
authors: Petra
authors: P
authors: Skare
authors: Lawrence O
authors: LO
authors: Klein
authors: Mark M
authors: MM
authors: Davis
authors: Chang-Zheng
authors: CZ
authors: Chen
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000737:chemistry / Q000276:immunology; D015536:Down-Regulation; D005786:Gene Expression Regulation; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D009036:Moths; D041681:NIH 3T3 Cells; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D009924:Organ Culture Techniques; D010455:Peptides / Q000276:immunology; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D045304:Cytochromes c; D010744:Phosphoric Monoester Hydrolases