Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran.
Iran J Allergy Asthma Immunol. 2023 Jun 16;22(3):299-311. 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.
T 细胞失调和向辅助性 T 细胞 2 反应的转变，增强肿瘤微环境的支持，有助于慢性淋巴细胞白血病中白血病 B 细胞的存活。白细胞介素（IL）-25 参与辅助性 T 细胞 2 反应的启动。IL-25 的信号转导始于异二聚体受体（IL-17RA/IL-17RB）。肿瘤微环境中 IL-25 的存在可能会影响周围肿瘤细胞环境中 T 细胞的支持作用。本研究旨在评估 IL-25 在 CLL 生物学中的作用。通过实时聚合酶链反应和流式细胞术评估了 9 例 CLL 患者和 9 例健康对照者分离的外周血单个核细胞（PBMC）中 CD3+和 CD19+细胞中的 IL-17RB 表达。使用磁性激活细胞分选（MACS）从 PBMC 中阳性富集 B 细胞。将 PBMC 和纯化的白血病 B 细胞与重组人 IL-25（20ng/ml）共培养 72 小时，然后通过 MTT 测定和 AnnexinV/7AAD 测定培养细胞的活力和凋亡。此外，通过流式细胞术测定 T 淋巴细胞和 T、B 细胞中 IL-17RB 的 CD69 表达水平。CLL 患者的 IL-17RB 表达基础水平明显高于对照组。此外，与健康对照者相比，CLL 患者在 IL-25 培养 72 小时后，IL-17RB+/CD3+、IL-17RB+/CD19+细胞和 CD69+/CD3+细胞的百分比增加。IL-25 还降低了肿瘤细胞的凋亡率。我们发现 IL-25 可以刺激 CLL 患者的 T 细胞，降低 B 细胞的死亡。这表明，IL-25 可能通过表达炎症受体（如 IL-17RB）在增强肿瘤细胞的存活中发挥作用，并且可能参与 CLL 的发生。
