Progranulin prevents regulatory NK cell cytotoxicity against antiviral T cells.
JCI Insight
; 4(17)2019 09 05.
Article
in En
| MEDLINE
| ID: mdl-31484831
ABSTRACT
`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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Killer Cells, Natural
/
T-Lymphocytes
/
Cytotoxicity, Immunologic
/
Progranulins
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
JCI Insight
Year:
2019
Type:
Article