Introduction: CD69 is an early activation marker expressed on T cells following activation and differentiation, and at sites of chronic inflammation. T cell dysfunction and a Th2 differentiation shift in B-cell chronic lymphocytic leukemia (B-CLL) contribute to disease progression. IL-17E, a pro-inflammatory cytokine present in the tumor microenvironment, promotes Th2-mediated immune responses through its receptor complex, IL-17RA/IL-17RB.

Objectives: This study investigates the impact of IL-17E on T cell activation and IL-17RB expression in CLL patients compared to healthy individuals to elucidate its role in immune dysregulation within the CLL microenvironment.

Methods: CD69 and IL-17RB expression on CD3+ T cells was assessed in peripheral blood mononuclear cells (PBMCs) from six CLL patients and six age- and sex-matched healthy controls using flow cytometry. PBMCs from CLL patients and healthy subjects were cultured in RPMI-1640 medium supplemented with 10% human AB+ serum (HABs) and recombinant human IL-17E for 72 h. The expression of CD69 and IL-17RB on CD3+ T cells was then evaluated by flow cytometry.

Results: Following treatment with IL-17E, a significant increase in CD69 expression was observed on CD3+ T cells from CLL patients compared to healthy donors. Additionally, IL-17RB expression on CD3+ T cells was significantly lower in patients than in healthy controls before treatment. However, after IL-17E treatment, IL-17RB levels were significantly increased in CLL CD3+ cells, surpassing those observed in normal CD3+ T cells.

Conclusion: IL-17E enhances T cell activation, as indicated by increased CD69 expression, and upregulates IL-17RB on CD3+ T cells in CLL patients. These findings suggest that IL-17E contributes to a pro-inflammatory tumor microenvironment, potentially promoting immune dysregulation and tumor survival. Further research is needed to explore the mechanisms underlying this signaling axis and its potential use in immune-based therapies for CLL.