Open AccessMicroRNA-29a attenuates CD8 T cell exhaustion and induces memory-like CD8 T cells during chronic infection
Author(s) -
Erietta Stelekati,
Zhongli Cai,
Sasikanth Manne,
Zeyu Chen,
Jean-Christophe Beltra,
Lance Buchness,
Xuebing Leng,
Svetlana Ristin,
Kito Nzingha,
Viktoriya Ekshyyan,
Christiiavi,
Mohamed S. Abdel-Hakeem,
Mohammed-Alkhatim Ali,
Sydney Drury,
Chi Wai Lau,
Gao Z,
Yuguang Ban,
Simon Zhou,
K. Mark Ansel,
Makoto Kurachi,
Martha S. Jordan,
Alejandro V. Villarino,
Shin Foong Ngiow,
E. John Wherry
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2106083119
Subject(s) - cytotoxic t cell , cd8 , immunology , immune system , biology , immunity , transcriptome , t cell , chronic infection , immunotherapy , microbiology and biotechnology , gene expression , genetics , gene , in vitro
Significance CD8 T cell exhaustion is a key underlying factor limiting immunity in chronic infections and cancer. Persistent antigen exposure antagonizes formation of functional memory CD8 T cells that provide long-term protection and, instead, drives the development of exhausted CD8 T cells (TEX ). Improving TEX persistence and function is a major goal for reinvigorating immune responses against chronic infections and tumors. Here, we identify miR-29a as a molecule that attenuates exhaustion and enhances persistence and function of TEX . Enforced expression of miR-29a alters TEX transcriptome, resulting in robust changes in molecular pathways governed by fundamental transcription factors and epigenetic modulators. Thus, enforced miR-29a expression enhances TEX responses, attenuates exhaustion, and represents a target for improving the outcome of immunotherapy.