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

• Published in: Iranian journal of allergy, asthma, and immunology asthma, and immunology, 2023, Vol.22 (3), p.299
• Main Authors: Pashaei, Mehrnoosh, Ghahremanfard, Farahnaz, Doulabi, Ehsan Manouchehri, Hemmati, Maral, Pak, Fatemeh, Kokhaei, Parviz
• Format: Article
• Language: English
• Subjects: Apoptosis; CD19 antigen; CD3 antigen; CD69 antigen; Cell activation; Cell culture; Cell death; Cell survival; Chronic lymphocytic leukemia; Flow cytometry; Interleukin-25; Leukemia; Leukocytes (mononuclear); Lymphocytes; Lymphocytes B; Lymphocytes T; Peripheral blood mononuclear cells; Signal transduction; T helper 2 cells; Tumor cells; Tumor microenvironment; Tumors
• ISSN: 1735-1502; 1735-5249; 1735-5249
• DOI: 10.18502/ijaai.v22i3.13058

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.