Schaffert, Steven A.;
Loh, Christina;
Wang, Song;
Arnold, Christopher P.;
Axtell, Robert C.;
Newell, Evan W.;
Nolan, Garry;
Ansel, K. Mark;
Davis, Mark M.;
Steinman, Lawrence;
Chen, Chang-Zheng
mir-181a-1/b-1 Modulates Tolerance through Opposing Activities in Selection and Peripheral T Cell Function
You can manage bookmarks using lists, please log in to your user account for this.
Media type:
E-Article
Title:
mir-181a-1/b-1 Modulates Tolerance through Opposing Activities in Selection and Peripheral T Cell Function
Contributor:
Schaffert, Steven A.;
Loh, Christina;
Wang, Song;
Arnold, Christopher P.;
Axtell, Robert C.;
Newell, Evan W.;
Nolan, Garry;
Ansel, K. Mark;
Davis, Mark M.;
Steinman, Lawrence;
Chen, Chang-Zheng
Published:
The American Association of Immunologists, 2015
Published in:
The Journal of Immunology, 195 (2015) 4, Seite 1470-1479
Language:
English
DOI:
10.4049/jimmunol.1401587
ISSN:
1550-6606;
0022-1767
Origination:
Footnote:
Description:
Abstract Understanding the consequences of tuning TCR signaling on selection, peripheral T cell function, and tolerance in the context of native TCR repertoires may provide insight into the physiological control of tolerance. In this study, we show that genetic ablation of a natural tuner of TCR signaling, mir-181a-1/b-1, in double-positive thymocytes dampened TCR and Erk signaling and increased the threshold of positive selection. Whereas mir-181a-1/b-1 deletion in mice resulted in an increase in the intrinsic reactivity of naive T cells to self-antigens, it did not cause spontaneous autoimmunity. Loss of mir-181a-1/b-1 dampened the induction of experimental autoimmune encephalomyelitis and reduced basal TCR signaling in peripheral T cells and their migration from lymph nodes to pathogenic sites. Taken together, these results demonstrate that tolerance can be modulated by microRNA gene products through the control of opposing activities in T cell selection and peripheral T cell function.