| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Axtell, Robert C. Steinman, Lawrence Loh, Christina Schaffert, Steven A. Chen, Chang-Zheng Wang, Song Nolan, Garry Ansel, K. Mark Arnold, Christopher P. Newell, Evan W. Davis, Mark M. |
| Description |
Author Affiliation: Schaffert SA ( Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305); Loh C ( Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305); Wang S ( Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305); Arnold CP ( Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305); Axtell RC ( Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305); Newell EW ( Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305); Nolan G ( Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305); Ansel KM ( Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143); Davis MM ( Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305); Steinman L ( Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305); Chen CZ ( Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305) |
| 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. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| DOI |
10.4049/jimmunol.1401587 |
| Journal |
The Journal of Immunology |
| Issue Number |
4 |
| Volume Number |
195 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2015-08-15 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Clonal Selection, Antigen-mediated Genetics Immunology Immune Tolerance Micrornas T-lymphocyte Subsets Metabolism Animals Autoimmunity Cell Movement Disease Models, Animal Dual Specificity Phosphatase 6 Encephalomyelitis, Autoimmune, Experimental Pathology Gene Deletion Immunization Lysophospholipids Map Kinase Signaling System Mice Mice, Knockout Oligonucleotides Rna Interference Receptors, Antigen, T-cell Signal Transduction Sphingosine Analogs & Derivatives Thymocytes Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
