MicroRNA-29a attenuates CD8 T cell exhaustion and induces memory-like CD8 T cells during chronic infection | Zendy

Erietta Stelekati | Zendy; Zhangying Cai | Zendy; Sasikanth Manne | Zendy; Zeyu Chen | Zendy; JeanChristophe Beltra | Zendy; Lance Buchness | Zendy; Xuebing Leng | Zendy; Svetlana Ristin | Zendy; Kito Nzingha | Zendy; Viktoriya Ekshyyan | Zendy; Christiiavi | Zendy; Mohamed S. Abdel-Hakeem | Zendy; Mohammed-Alkhatim Ali | Zendy; Sydney Drury | Zendy; Chi Wai Lau | Zendy; Zhen Gao | Zendy; Yuguang Ban | Zendy; Simon K. Zhou | Zendy; K. Mark Ansel | Zendy; Makoto Kurachi | Zendy; Martha S. Jordan | Zendy; Alejandro V. Villarino | Zendy; Shin Foong Ngiow | Zendy; E. John Wherry | Zendy

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MicroRNA-29a attenuates CD8 T cell exhaustion and induces memory-like CD8 T cells during chronic infection

Author(s) -

Erietta Stelekati,

Zhangying Cai,

Sasikanth Manne,

Zeyu Chen,

JeanChristophe Beltra,

Lance Buchness,

Xuebing Leng,

Svetlana Ristin,

Kito Nzingha,

Viktoriya Ekshyyan,

Christiiavi,

Mohamed S. Abdel-Hakeem,

Mohammed-Alkhatim Ali,

Sydney Drury,

Chi Wai Lau,

Zhen Gao,

Yuguang Ban,

Simon K. 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

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.

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