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 viral infection has remained unexplored. Here, we genetically ablated expression of the type I interferon-α receptor (Ifnar) 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.

Islander, Ulrika,1975Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Krefting Research Centre,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xislul (author)
Lütge, Mechthild (author)
Cheng, Hung-Wei (author)
Onder, Lucas (author)
Ring, Sandra S (author)
De Martin, Angelina (author)
Novkovic, Mario (author)
Colston, Julia (author)
Gil-Cruz, Cristina (author)
Ludewig, Burkhard (author)
Göteborgs universitetCentre for Bone and Arthritis Research (creator_code:org_t)

By the author/editor: Perez-Shibayama, ...; Islander, Ulrika ...; Lütge, Mechthild; Cheng, Hung-Wei; Onder, Lucas; Ring, Sandra S; show more...; De Martin, Angel ...; Novkovic, Mario; Colston, Julia; Gil-Cruz, Cristi ...; Ludewig, Burkhar ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Immunology in th ...

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