Year: 2025
Type: article
Abstract: Description TANK-binding kinase 1 (TBK1) is a serine/threonine protein kinase that serves as a signaling hub in pathways associated with inflammation and pathogen detection through pattern recognition receptors. Although TBK1’s role in innate immunity is well established, its role in CD8+ T cell differentiation and exhaustion remains unclear. Stem-like CD8+ T cells are crucial for maintaining the long-term T cell responses required to control chronic infections and cancers. Here, we identify TBK1 as a positive regulator of long-term CD8+ T cell responses. The CD8+ T cell-specific ablation of TBK1 impairs the differentiation of stem-like T cells during chronic viral infection. Although TBK1-deficient CD8+ T cells show an increased percentage of proliferating cells at early time points, they fail to persist in the spleen and brain. Single-cell RNA sequencing (scRNA-seq) reveals that TBK1 deficiency in CD8+ T cells impairs responses to type I interferons, TCR signaling, and T cell migration. We are actively investigating these pathways to further elucidate their crosstalk with TBK1. Our findings highlight a pivotal role for TBK1 in regulating the long-term CD8+ T cell response. Funding Sources Supported by NIH/NIA AG-083398; NIAID AI-158294; DOD Award HT9425-23-1-0801 (Proposal KC220216) Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)
Source: The Journal of Immunology
Authors: Jonathan Hoar, Ying Luo, Tuoqi Wu, Chen Yao
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4416447290
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