| Literature DB >> 35446623 |
Erietta Stelekati1,2, Zhangying Cai3,4, Sasikanth Manne3,4, Zeyu Chen3,4, Jean-Christophe Beltra3,4, Lance Alec Buchness1,2, Xuebing Leng1,2, Svetlana Ristin1,2, Kito Nzingha3,4, Viktoriya Ekshyyan3,4, Christina Niavi3,4, Mohamed S Abdel-Hakeem3,4, Mohammed-Alkhatim Ali3,4, Sydney Drury4,5, Chi Wai Lau3,4, Zhen Gao2,6, Yuguang Ban2,7, Simon K Zhou8,9, K Mark Ansel8,9, Makoto Kurachi3,4, Martha S Jordan4,5, Alejandro V Villarino1,2, Shin Foong Ngiow3,4, E John Wherry3,4.
Abstract
CD8 T cells mediate protection against intracellular pathogens and tumors. However, persistent antigen during chronic infections or cancer leads to T cell exhaustion, suboptimal functionality, and reduced protective capacity. Despite considerable work interrogating the transcriptional regulation of exhausted CD8 T cells (TEX), the posttranscriptional control of TEX remains poorly understood. Here, we interrogated the role of microRNAs (miRs) in CD8 T cells responding to acutely resolved or chronic viral infection and identified miR-29a as a key regulator of TEX. Enforced expression of miR-29a improved CD8 T cell responses during chronic viral infection and antagonized exhaustion. miR-29a inhibited exhaustion-driving transcriptional pathways, including inflammatory and T cell receptor signaling, and regulated ribosomal biogenesis. As a result, miR-29a fostered a memory-like CD8 T cell differentiation state during chronic infection. Thus, we identify miR-29a as a key regulator of TEX and define mechanisms by which miR-29a can divert exhaustion toward a more beneficial memory-like CD8 T cell differentiation state.Entities:
Keywords: CD8 T cells; exhaustion; microRNA
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Year: 2022 PMID： 35446623 PMCID： PMC9169946 DOI： 10.1073/pnas.2106083119
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 12.779