| First Author | Huang A | Year | 2019 |
| Journal | JCI Insight | Volume | 4 |
| Issue | 17 | PubMed ID | 31484831 |
| Mgi Jnum | J:296734 | Mgi Id | MGI:6469761 |
| Doi | 10.1172/jci.insight.129856 | Citation | Huang A, et al. (2019) Progranulin prevents regulatory NK cell cytotoxicity against antiviral T cells. JCI Insight 4(17) |
| abstractText | `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. |
