Adna Hassan

Metabolic dysfunction-associated steatohepatitis (MASH) is a growing concern affecting about 6% of the US population. MASH is associated with an accumulation of fat in the liver which can lead to inflammation and fibrosis. It is gradually becoming evident that T lymphocytes contribute to the pathogenic immune response in MASH. Our unpublished data reveals heterogeneity within the liver CD4 T cell compartment when comparing healthy and MASH mice. Previously, we identified that there is a distinction among the CD4 T cell populations, particularly, the pro-inflammatory Th1 subtype of CD4 T cell was upregulated in the MASH liver. It is essential to understand whether the changes in the CD4 T cell landscape are systemic or localized to the liver. Therefore, we sought to investigate the CD4 T cell landscape in the blood using a murine MASH model.​ Wild-type mice were fed either a MASH-inducing diet high in Fat, Fructose, and Cholesterol (FFC) or chow for 24 weeks. Thereafter, CD4 T cells were isolated from the peripheral blood and were subjected to mass cytometry by time-of-flight (CyTOF). An unsupervised clustering algorithm identified 18 unique CD4 T cell clusters. We observed that MASH peripheral CD4 T cells had a lower frequency of clusters of central memory T cells, and naïve T cells when compared to chow-fed mice. Additionally, Th1 and Treg subtypes were more abundant in clusters only in FFC-fed mice. ​Here, we demonstrate that the changes in CD4 T cell homeostasis in MASH mouse livers are replicated in the blood.