| First Author | Duhalde Vega M | Year | 2022 |
| Journal | Sci Adv | Volume | 8 |
| Issue | 38 | Pages | eabn6545 |
| PubMed ID | 36129987 | Mgi Jnum | J:331762 |
| Mgi Id | MGI:7345058 | Doi | 10.1126/sciadv.abn6545 |
| Citation | Duhalde Vega M, et al. (2022) PD-1/PD-L1 blockade abrogates a dysfunctional innate-adaptive immune axis in critical beta-coronavirus disease. Sci Adv 8(38):eabn6545 |
| abstractText | Severe COVID-19 is associated with hyperinflammation and weak T cell responses against SARS-CoV-2. However, the links between those processes remain partially characterized. Moreover, whether and how therapeutically manipulating T cells may benefit patients are unknown. Our genetic and pharmacological evidence demonstrates that the ion channel TMEM176B inhibited inflammasome activation triggered by SARS-CoV-2 and SARS-CoV-2-related murine beta-coronavirus. Tmem176b(-/-) mice infected with murine beta-coronavirus developed inflammasome-dependent T cell dysfunction and critical disease, which was controlled by modulating dysfunctional T cells with PD-1 blockers. In critical COVID-19, inflammasome activation correlated with dysfunctional T cells and low monocytic TMEM176B expression, whereas PD-L1 blockade rescued T cell functionality. Here, we mechanistically link T cell dysfunction and inflammation, supporting a cancer immunotherapy to reinforce T cell immunity in critical beta-coronavirus disease. |
