Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 3 2023 06 16 299 311 Mehrnoosh Pashei 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 AND Department of Oncology-Pathology, BioClinicum, Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden 2022 10 15 2023 03 02 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. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3676 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3676/1946