| First Author | Paterson CW | Year | 2024 |
| Journal | Immunohorizons | Volume | 8 |
| Issue | 1 | Pages | 74-88 |
| PubMed ID | 38226924 | Mgi Jnum | J:360606 |
| Mgi Id | MGI:7834553 | Doi | 10.4049/immunohorizons.2300060 |
| Citation | Paterson CW, et al. (2024) CTLA-4 Checkpoint Inhibition Improves Sepsis Survival in Alcohol-Exposed Mice. Immunohorizons 8(1):74-88 |
| abstractText | Chronic alcohol use increases morbidity and mortality in the setting of sepsis. Both chronic alcohol use and sepsis are characterized by immune dysregulation, including overexpression of T cell coinhibitory molecules. We sought to characterize the role of CTLA-4 during sepsis in the setting of chronic alcohol exposure using a murine model of chronic alcohol ingestion followed by cecal ligation and puncture. Results indicated that CTLA-4 expression is increased on CD4+ T cells isolated from alcohol-drinking septic mice as compared with either alcohol-drinking sham controls or water-drinking septic mice. Moreover, checkpoint inhibition of CTLA-4 improved sepsis survival in alcohol-drinking septic mice, but not water-drinking septic mice. Interrogation of the T cell compartments in these animals following pharmacologic CTLA-4 blockade, as well as following conditional Ctla4 deletion in CD4+ T cells, revealed that CTLA-4 deficiency promoted the activation and proliferation of effector regulatory T cells and the generation of conventional effector memory CD4+ T cells. These data highlight an important role for CTLA-4 in mediating mortality during sepsis in the setting of chronic alcohol exposure and may inform future approaches to develop targeted therapies for this patient population. |
