IL-2 signaling shapes patterns of Interferon Regulatory Factor 8 expression in CD8 T cells 4824
Year: 2025
Type: article
Abstract: Description Two closely related members of the interferon regulatory factor (IRF) family of transcription factors, IRF4 and IRF8, have been described to reinforce divergent cell states in dendritic cells, B cells and macrophages. Although IRF4 has been recognized to critically support CD8 T cell differentiation, little is known mechanistically of the role of IRF8 in this process. Using OT-1 CD8 T cells, we show that unlike IRF4, IRF8 exhibits a biphasic pattern of induction upon T-Cell Receptor (TCR) engagement that is highly sensitive to JAK-STAT inhibition and less shaped by TCR signal strength. At the peak of OVA-expressing Listeria monocytogenes infection, OT-1 cells that produced IL-2 upon restimulation expressed more IRF4 and less IRF8 than their non-IL-2 producing counterparts (IL-2 responders). In the absence of TCR stimulation, ex-vivo Cytotoxic T Lymphocytes rested in IL-2 alone induced IRF8 but not IRF4 in a dose-dependent manner. In models of antigen persistence such as MC38 tumors, preliminary data indicate an enrichment of IRF8-expressing CD8+ Tumor Infiltrating Lymphocytes (TILs) in the Granzyme B expressing cells, while no such enrichment was observed for IRF4. In summary, the response of IRF8 to IL-2 signaling and its prevalence in tumor infiltrating lymphocytes suggests its potential as a target for immunotherapy. Funding Sources Supported by NIH R01AI132419-03 Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)
Source: The Journal of Immunology
Authors: Uddeep Chaudhury, Alayna M. Rosales, Zoe K. Bedrosian, Jared Klarquist, Leslie J. Berg
Institution: University of Colorado Anschutz
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
Funder: National Institutes of Health
OpenAlex ID: W4416448669
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