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

Christian Perez Shibayama, Ulrika Islander, Mechthild Lütge, Hung-Wei Cheng, Lucas Onder, Sandra Ring, Angelina De Martin, Mario Novkovic, Julia Colston, Cristina Gil Cruz & Burkhard Ludewig

abstract 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.
   
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Abstract: http://immunology.sciencemag.org/cgi/content/abstract/5/51/eabb7066?ijkey=SVyn0z7cc6os.&keytype=ref&siteid=immunology

Reprint: http://immunology.sciencemag.org?ijkey=SVyn0z7cc6os.&keytype=ref&siteid=immunology

Full text: http://immunology.sciencemag.org/cgi/content/full/5/51/eabb7066?ijkey=SVyn0z7cc6os.&keytype=ref&siteid=immunology
   
citation Perez Shibayama C, Islander U, Lütge M, Cheng H W, Onder L, Ring S, De Martin A, Novkovic M, Colston J, Gil Cruz C, Ludewig B. Type I interferon signaling in fibroblastic reticular cells prevents exhaustive activation of antiviral CD8 T cells. Sci Immunol 2020; 5:.
   
type journal paper/review (English)
date of publishing 11-9-2020
journal title Sci Immunol (5/51)
ISSN electronic 2470-9468
PubMed 32917792
DOI 10.1126/sciimmunol.abb7066
link http://immunology.sciencemag.org/cgi/content/summary/5/51/eabb7066?ijkey=SVyn0z7cc6os.&keytype=ref&siteid=immunology
contact Burkhard Ludewig