Work

IL-10 signaling in CD8+ T cell memory formation and differentiation in different infection models 4067

Year: 2025

Type: article

Abstract: Description IL-10 is a cytokine with immune and non-immune homeostatic functions generally recognized as anti-inflammatory, however the role of IL-10 receptor (IL-10R) expression on CD8+ T cells is unclear. Studies in mouse models indicate a discordant role for IL-10R signaling for memory CD8+ T cell generation as it is beneficial in LCMV Armstrong (LCMV) infection but detrimental to memory formation following Listeria monocytogenes (Lm) infection. These studies relied on germline or T cell specific knockout of IL10R or antibody-based blockade complicating interpretation due to IL-10 signaling effects on T cell development and/or other cell types. We ablated Il10ra and Stat3 in naive P14 TCR transgenic (P14) CD8+ T cells by CRISPR-Cas9 gene editing to test whether IL-10R signaling is required for forming memory CD8+ T cells after LCMV or Lm-gp33 infection. Our data suggest Il10ra-/- CD8+ T cells are at a modest disadvantage compared to co-transferred control cells in the blood at day 30 post infection and Stat3-/- cells at Day 7 and Day 31 post LCMV have a greater disadvantage compared to Il10ra-/- cells implicating other cytokines (potentially including IL-21) that activate STAT3. A trend toward loss of Il10ra-/- cells in the liver and IEL compared to spleen and blood suggests the need for IL-10R stimulation differs for circulating versus tissue resident memory CD8+ T cells. This work will define how the role of IL-10R signaling may vary by CD8+ T cell memory subset and infection model. Funding Sources NIH/NIAID R01 AI038903 Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.1797

Authors: Sarah M. Wall, Taylor A. DePauw, Erin D. Lucas, William J. Valente, Katharine E. Block, Stephen Jameson

Institution: University of Minnesota

Language: English

Topic: T-cell and B-cell Immunology

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: National Institutes of Health, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases