Type I interferon signaling in fibroblastic reticular cells prevents exhaustive activation of antiviral CD8 + T cells

Fibroblastic reticular cells (FRCs) are stromal cells that actively promote the induction of immune responses by coordinating the interaction of innate and adaptive immune cells. However, whether and to which extent immune cell activation is determined by lymph node FRC reprogramming during acute vi...

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Bibliographic Details
Published in:Science immunology 2020-09, Vol.5 (51)
Main Authors: Perez-Shibayama, Christian, Islander, Ulrika, Lütge, Mechthild, Cheng, Hung-Wei, Onder, Lucas, Ring, Sandra S, De Martin, Angelina, Novkovic, Mario, Colston, Julia, Gil-Cruz, Cristina, Ludewig, Burkhard
Format: Article
Language:English
Subjects:
Animals
CD8-Positive T-Lymphocytes - immunology
Cell Line
Fibroblasts - immunology
Immunologi inom det medicinska området
Immunology in the medical area
Interferon Type I - immunology
Interferon-gamma - immunology
Lymphocytic Choriomeningitis - immunology
Lymphocytic choriomeningitis virus
Mice, Inbred C57BL
Mice, Transgenic
Receptor, Interferon alpha-beta - genetics
Receptor, Interferon alpha-beta - immunology
Signal Transduction
Stromal Cells - immunology
Tumor Necrosis Factor-alpha - immunology
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Summary:Fibroblastic reticular cells (FRCs) are stromal cells that actively promote the induction of immune responses by coordinating the interaction of innate and adaptive immune cells. However, whether and to which extent immune cell activation is determined by lymph node FRC reprogramming during acute viral infection has remained unexplored. Here, we genetically ablated expression of the type I interferon-α receptor ( ) in Ccl19-Cre cells and found that sensing of type I interferon imprints an antiviral state in FRCs and thereby preserves myeloid cell composition in lymph nodes of naive mice. During localized lymphocytic choriomeningitis virus infection, IFNAR signaling precipitated profound phenotypic adaptation of all FRC subsets enhancing antigen presentation, chemokine-driven immune cell recruitment, and immune regulation. The IFNAR-dependent shift of all FRC subsets toward an immunostimulatory state reduced exhaustive CD8 T cell activation. In sum, these results unveil intricate circuits underlying type I IFN sensing in lymph node FRCs that enable protective antiviral immunity.
ISSN:2470-9468
2470-9468
DOI:10.1126/SCIIMMUNOL.ABB7066