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miR-181a is an intrinsic modulator of T cell sensitivity and selection.

Publication ,  Journal Article
Li, Q-J; Chau, J; Ebert, PJR; Sylvester, G; Min, H; Liu, G; Braich, R; Manoharan, M; Soutschek, J; Skare, P; Klein, LO; Davis, MM; Chen, C-Z
Published in: Cell
April 6, 2007

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.

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Published In

Cell

DOI

ISSN

0092-8674

Publication Date

April 6, 2007

Volume

129

Issue

1

Start / End Page

147 / 161

Location

United States

Related Subject Headings

  • Thymus Gland
  • T-Lymphocytes
  • Signal Transduction
  • Receptors, Antigen, T-Cell
  • Phosphoric Monoester Hydrolases
  • Peptides
  • Organ Culture Techniques
  • Oligonucleotides, Antisense
  • NIH 3T3 Cells
  • Moths
 

Citation

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MLA
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Li, Q.-J., Chau, J., Ebert, P. J. R., Sylvester, G., Min, H., Liu, G., … Chen, C.-Z. (2007). miR-181a is an intrinsic modulator of T cell sensitivity and selection. Cell, 129(1), 147–161. https://doi.org/10.1016/j.cell.2007.03.008
Li, Qi-Jing, Jacqueline Chau, Peter J. R. Ebert, Giselle Sylvester, Hyeyoung Min, Gwen Liu, Ravi Braich, et al. “miR-181a is an intrinsic modulator of T cell sensitivity and selection.Cell 129, no. 1 (April 6, 2007): 147–61. https://doi.org/10.1016/j.cell.2007.03.008.
Li Q-J, Chau J, Ebert PJR, Sylvester G, Min H, Liu G, et al. miR-181a is an intrinsic modulator of T cell sensitivity and selection. Cell. 2007 Apr 6;129(1):147–61.
Li, Qi-Jing, et al. “miR-181a is an intrinsic modulator of T cell sensitivity and selection.Cell, vol. 129, no. 1, Apr. 2007, pp. 147–61. Pubmed, doi:10.1016/j.cell.2007.03.008.
Li Q-J, Chau J, Ebert PJR, Sylvester G, Min H, Liu G, Braich R, Manoharan M, Soutschek J, Skare P, Klein LO, Davis MM, Chen C-Z. miR-181a is an intrinsic modulator of T cell sensitivity and selection. Cell. 2007 Apr 6;129(1):147–161.
Journal cover image

Published In

Cell

DOI

ISSN

0092-8674

Publication Date

April 6, 2007

Volume

129

Issue

1

Start / End Page

147 / 161

Location

United States

Related Subject Headings

  • Thymus Gland
  • T-Lymphocytes
  • Signal Transduction
  • Receptors, Antigen, T-Cell
  • Phosphoric Monoester Hydrolases
  • Peptides
  • Organ Culture Techniques
  • Oligonucleotides, Antisense
  • NIH 3T3 Cells
  • Moths