IL-25 Impact on Malignant B Cells Survival and T Cells Activation  in Chronic Lymphocytic Leukemia

Mehrnoosh Pashaei; Farahnaz Ghahremanfard; Ehsan Manouchehri Doulabi; Maral Hemmati; Fatemeh Pak; Parviz Kokhaei

doi:10.18502/ijaai.v22i3.13058

Mehrnoosh Pashaei Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Farahnaz Ghahremanfard Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran
Ehsan Manouchehri Doulabi Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
Maral Hemmati Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran
Fatemeh Pak Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran
Parviz Kokhaei Department of Immunology, Arak University of Medical Sciences, Arak, Iran

DOI: https://doi.org/10.18502/ijaai.v22i3.13058

Keywords: Chronic lymphocytic leukemia; Interleukin-25; Tumor microenvironment; T helper 2 cells

Abstract

T cell dysregulation and shift to T helper 2 responses, boosting tumor microenvironment support, contributes to the survival of leukemic B cells in Chronic Lymphocytic Leukemia. Interleukin (IL)-25 is involved in the initiation of T helper 2 cell responses. Signal transduction of IL-25 begins with the heterodimer receptor (IL-17RA/IL-17RB). The presence of IL-25 in the tumor microenvironment may affect the supportive effects of T cells in the surrounding tumor cell environment. The purpose of this study was to evaluate the role of IL-25 in the biology of CLL.

IL-17RB expression in CD3⁺ and CD19⁺ cells was assessed in isolated peripheral blood mononuclear cells (PBMCs) of nine CLL patients and nine healthy subjects by real-time polymerase chain reaction and flow cytometry. B cells were positively enriched from PBMCs using magnetic-activated cell sorting (MACS). PBMCs and purified leukemic B cells were cultured with recombinant human IL-25 (20ng/ml) for 72 hours, then the viability and apoptosis of cultured cells were measured by MTT assay and AnnexinV/7AAD. Furthermore, the levels of CD69 expression on T lymphocytes and IL-17RB in T and B cells were determined by flow cytometry.

The basal level of IL-17RB expression in CLL patients was significantly higher than that in control individuals. In addition, the percentage of IL-17RB⁺/CD3⁺, IL-17RB⁺/CD19⁺ cells and CD69⁺/CD3⁺ cells increased after 72 hours of culture with IL-25 in CLL patients compared to healthy subjects. IL-25 also reduces the apoptosis rate of tumor cells.

We found that IL-25 could stimulate T cells in CLL patients and lower B cell death. This suggests that IL-25 might have a role in enhancing the survival of tumor cell by expressing receptors for inflammation, such as IL-17RB, and might be involved in the development of CLL.