Angiopoietin-1 Receptor (CD202b) Identifies IL-4-secreting Human Invariant Natural Killer Cells

The relationship between lipid-induced stress in human hepatocytes and inflammation in metabolic dysfunction-associated steatotic liver disease (MASLD) remains unclear; however, innate immunity is an important factor in disease progression. The discovery that IL-4+iNKT cells were overrepresented amongst intrahepatic lymphocytes from patients with steatotic liver disease suggests a pathogenic role, but their immunological function is uncertain. To study this rare population, we needed a reliable marker set that allows us to isolate living cells. Here, we report a combination of cell surface markers that can accurately predict IL-4 production by in vitro-expanded iNKT cells. Our multivariate models identify several combinations of up to 5 markers that reliably distinguish IL-4+iNKT cells. CD202b (angiopoietin-1 receptor, Tie2) emerges as a predominant factor in these predictions. We conclude that the CD202bhigh CD25low phenotype predicts IL-4+iNKT cells in vitro with an accuracy of 93.02±2.61%, a sensitivity of 75.22±17.23% and a specificity of 95.01±4.75%. Hence, we are now able to detect and sort living, in vitro-expanded IL-4+iNKT cells without directly measuring IL-4 production.

Publication History

Article published online:
20 January 2025