Adrenergic signaling controls early transcriptional programs during CD8+ T cell responses to viral infection.

Autor: Estrada LD; Department of Immunology, UT Southwestern Medical Center, Dallas, TX, United States of America., Ağaç Çobanoğlu D; Department of Immunology, UT Southwestern Medical Center, Dallas, TX, United States of America., Wise A; Encodia Inc., San Diego, CA, United States of America., Maples RW; Department of Immunology, UT Southwestern Medical Center, Dallas, TX, United States of America., Çobanoğlu MC; Department of Bioinformatics, UT Southwestern Medical Center, Dallas, TX, United States of America., Farrar JD; Department of Immunology, UT Southwestern Medical Center, Dallas, TX, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2022 Aug 09; Vol. 17 (8), pp. e0272017. Date of Electronic Publication: 2022 Aug 09 (Print Publication: 2022).
DOI: 10.1371/journal.pone.0272017
Abstrakt: Norepinephrine is a key sympathetic neurotransmitter, which acts to suppress CD8 + T cell cytokine secretion and lytic activity by signaling through the β2-adrenergic receptor (ADRB2). Although ADRB2 signaling is considered generally immunosuppressive, its role in regulating the differentiation of effector T cells in response to infection has not been investigated. Using an adoptive transfer approach, we compared the expansion and differentiation of wild type (WT) to Adrb2-/- CD8 + T cells throughout the primary response to vesicular stomatitis virus (VSV) infection in vivo. We measured the dynamic changes in transcriptome profiles of antigen-specific CD8 + T cells as they responded to VSV. Within the first 7 days of infection, WT cells out-paced the expansion of Adrb2-/- cells, which correlated with reduced expression of IL-2 and the IL-2Rα in the absence of ADRB2. RNASeq analysis identified over 300 differentially expressed genes that were both temporally regulated following infection and selectively regulated in WT vs Adrb2-/- cells. These genes contributed to major transcriptional pathways including cytokine receptor activation, signaling in cancer, immune deficiency, and neurotransmitter pathways. By parsing genes within groups that were either induced or repressed over time in response to infection, we identified three main branches of genes that were differentially regulated by the ADRB2. These gene sets were predicted to be regulated by specific transcription factors involved in effector T cell development, such as Tbx21 and Eomes. Collectively, these data demonstrate a significant role for ADRB2 signaling in regulating key transcriptional pathways during CD8 + T cells responses to infection that may dramatically impact their functional capabilities and downstream memory cell development.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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