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Document Type
Poster
Publication Date
Fall 10-1-2026
Abstract
Obesity is a pandemic and represents a major risk factor for the development of metabolic dysfunction-associated steatotic liver disease (MASLD). The lack of effective therapies for MASLD is attributed to limited knowledge of disease etiopathogenesis. The processes that regulate MASLD development and progression are complex and poorly understood. Proinflammatory immune responses are considered a critical causative link between obesity and MASLD pathogenesis. Emerging evidence suggests an important role for innate and adaptive immune cells (e.g., macrophages, NKT cells, and T cells) in the development and progression of MASLD. Furthermore, proinflammatory cytokines produced by these immune cells are directly linked with MASLD pathogenesis. Particularly, interleukin 21 (IL-21), a cytokine produced by CD4+ T cells, CD8+ T cells, and NKT cells with pleiotropic functions, including cellular proliferation, survival, and metabolism, has been associated with MASLD. Meanwhile, the IL-21 receptor (IL-21R) is not exclusively expressed by immune cells (e.g., Kupffer cells, macrophages, NKT, and CD4+ T cells) and is found on adipocytes and endothelial cells. However, despite the apparent biological and clinical significance, the cellular source and targets by which IL-21 promotes MASLD pathogenesis remain unclear and represent a major knowledge gap. Our novel data indicate that: (i) increased circulating levels of IL-21, and increased liver IL21 and IL21R mRNA levels are observed in humans with MASLD compared to metabolically healthy obese and lean counterparts are observed in humans with MASLD compared to metabolically healthy obese and lean counterparts; and (ii) IL-21-/- mice fed a high-fat diet, compared to wild-type controls, exhibit similar weight gain and visceral adiposity but are protected from hepatic steatosis and hepatocellular damage. Further, our characterization of the hepatic IL-21-producing cells revealed that: (iv) the number of IL-21-producing cells progressively increases in the liver of WT mice fed a high-fat diet; (v) hepatic CD4 T cells are the main producers of IL-21 in this setting and they were present in the liver. These findings provide insight into the immunopathogenic mechanism of MASLD progression and will provide the foundation for the development of future therapeutic approaches.
Department
Gastroenterology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
Project Mentor
Dr. Maria E. Moreno-Fernandez
Recommended Citation
Loh, Jonathan D. '27; Cuervo-Jiminez, Hayde K.; Lampe, Kristin; and Gordarova, Alzbeta, "Contribution of IL-21-Producing Cells to Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Progression" (2026). Annual Student Research Poster Session. 250.
https://scholarship.depauw.edu/srfposters/250
Funding and Acknowledgements
This work was supported by the National Institutes of Health (NIH) R01 DK146906 (to M.E.M.-F.), R01 HL167200 (associated with M.E.M.-F.) and R21 AI200165 (to CoPI M.E.M.-F. ). Cincinnati Children’s Hospital Medical Center Digestive Health Center P30 DK078392 (associated with M.E.M.-F.); American Liver Foundation FP00014179 (to M.E.M.-F.). M.E.M.-F. = Maria E. Moreno-Fernandez