Progranulin prevents regulatory NK cell cytotoxicity against antiviral T cells

`NK cell-mediated regulation of antigen-specific T cells can contribute to and exacerbate chronic viral infection, but the protective mechanisms against NK cell-mediated attack on T cell immunity are poorly understood. Here, we show that progranulin (PGRN) can reduce NK cell cytotoxicity through red...

Full description

Saved in:
Bibliographic Details
Published in:JCI insight 2019-09, Vol.4 (17)
Main Authors: Huang, Anfei, Shinde, Prashant V, Huang, Jun, Senff, Tina, Xu, Haifeng C, Margotta, Cassandra, Häussinger, Dieter, Willnow, Thomas E, Zhang, Jinping, Pandyra, Aleksandra A, Timm, Jörg, Weggen, Sascha, Lang, Karl S, Lang, Philipp A
Format: Article
Language:English
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:`NK cell-mediated regulation of antigen-specific T cells can contribute to and exacerbate chronic viral infection, but the protective mechanisms against NK cell-mediated attack on T cell immunity are poorly understood. Here, we show that progranulin (PGRN) can reduce NK cell cytotoxicity through reduction of NK cell expansion, granzyme B transcription, and NK cell-mediated lysis of target cells. Following infection with the lymphocytic choriomeningitis virus (LCMV), PGRN levels increased - a phenomenon dependent on the presence of macrophages and type I IFN signaling. Absence of PGRN in mice (Grn-/-) resulted in enhanced NK cell activity, increased NK cell-mediated killing of antiviral T cells, reduced antiviral T cell immunity, and increased viral burden, culminating in increased liver immunopathology. Depletion of NK cells restored antiviral immunity and alleviated pathology during infection in Grn-/- mice. In turn, PGRN treatment improved antiviral T cell immunity. Taken together, we identified PGRN as a critical factor capable of reducing NK cell-mediated attack of antiviral T cells.
ISSN:2379-3708
2379-3708
DOI:10.1172/jci.insight.129856