Journal article
Long-Term Persistence of Exhausted CD8 T Cells in Chronic Infection Is Regulated by MicroRNA-155
Cell reports (Cambridge), v 23(7), pp 2142-2156
15 May 2018
PMID: 29768211
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Persistent viral infections and tumors drive development of exhausted T (T-EX) cells. In these settings, T-EX cells establish an important host-pathogen or host-tumor stalemate. However, T-EX cells erode over time, leading to loss of pathogen or cancer containment. We identified microRNA (miR)-155 as a key regulator of sustained T-EX cell responses during chronic lymphocytic choriomeningitis virus (LCMV) infection. Genetic deficiency of miR-155 ab-lated CD8 T cell responses during chronic infection. Conversely, enhanced miR-155 expression promoted expansion and long-term persistence of T-EX cells. However, rather than strictly antagonizing exhaustion, miR-155 promoted a terminal T-EX cell subset. Transcriptional profiling identified coordinated control of cell signaling and transcription factor pathways, including the key AP-1 family member Fosl2. Overexpression of Fosl2 reversed the miR-155 effects, identifying a link between miR-155 and the AP-1 transcriptional program in regulating T-EX cells. Thus, we identify a mechanism of miR-155 regulation of T-EX cells and a key role for Fosl2 in T cell exhaustion.
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Details
- Title
- Long-Term Persistence of Exhausted CD8 T Cells in Chronic Infection Is Regulated by MicroRNA-155
- Creators
- Erietta Stelekati - University of PennsylvaniaZeyu Chen - University of PennsylvaniaSasikanth Manne - University of PennsylvaniaMakoto Kurachi - University of PennsylvaniaMohammed-Alkhatim Ali - University of PennsylvaniaKeith Lewy - University of PennsylvaniaZhangying Cai - College Station Medical CenterKito Nzingha - University of PennsylvaniaLaura M. McLane - University of PennsylvaniaJennifer L. Hope - Drexel UniversityAdam J. Fike - Drexel UniversityPeter D. Katsikis - Erasmus MCE. John Wherry - University of Pennsylvania
- Publication Details
- Cell reports (Cambridge), v 23(7), pp 2142-2156
- Publisher
- Elsevier
- Number of pages
- 15
- Grant note
- R01AI115712 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) Parker Institute for Cancer Immunotherapy AI117718; AI105343; AI112521; AI082630; AI115712; AI117950; AI108545 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000432455600021
- Scopus ID
- 2-s2.0-85047145332
- Other Identifier
- 991021448176504721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Cell Biology