In Vivo Suppression of Autophagy via Lentiviral shRNA Targeting Atg5 Improves Lupus-Like Syndrome.

In Vivo Suppression of Autophagy via Lentiviral shRNA Targeting Atg5 Improves Lupus-Like Syndrome.
Biomed Res Int. 2020;2020:8959726
Authors: Liu CJ, Tang SJ, Chou CC, Sun GH, Sun KH
Abstract
In both mouse models and clinical patients with lupus, autophagy levels were significantly elevated and correlated with disease activity. Furthermore, autophagy can promote the survival of B and T cells, plasma cell differentiation, and antibody production. These results suggest that autophagy may promote the progression of lupus by regulating the survival of autoreactive immune cells. Therefore, we aimed at studying whether suppressing autophagy can modulate lupus progression in vivo. First, we found that the autophagy levels in splenocytes and lymphocytes of peripheral blood (PB) were elevated and positively correlated with disease severity in lupus-prone mice. The shAtg5-lentivirus, which effectively inhibits autophagy in vitro, was then injected into the lupus-prone mice. Autophagy levels in lymph node cells and PB lymphocytes were reduced following Atg5 suppression. We also found that lymphadenopathy and the numbers of plasma cells, CD4-CD8-, and CD4+ T cells decreased in mice treated with the shAtg5-lentivirus. The mice treated with shAtg5-lentivirus exhibited lower levels of proteinuria, serum anti-dsDNA antibody, B-cell activating factor (BAFF), and glomerular immune complex deposition. Therefore, targeting autophagy to moderate overacti...

Source: Biomed Res - May 30, 2020 Category: Research Authors: Liu CJ, Tang SJ, Chou CC, Sun GH, Sun KH Tags: Biomed Res Int Source Type: research