Ghahramanipour Zahra, Naseri Bahar, Mardi Amirhossein, Sohrabi Sepideh, Masoumi Javad, Baghbani Elham, Karimzadeh Hadi, Baradaran Behzad
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Immunol Res. 2024 Dec 11;73(1):6. doi: 10.1007/s12026-024-09579-1.
Arginine vasopressin (AVP) has disparate impacts on immune responses by divergent receptors on cells including DCs. This study was conducted with the aim of investigating the impact of AVP on the maturation and expression of the inhibitory immune checkpoint molecules in tolerogenic monocyte-derived DCs. CD14 marker was used to separate monocytes from peripheral blood mononuclear cells (PBMCs) by MACS method. To differentiate monocytes from DCs, we utilized GM-CSF and IL-4 cytokines. Tolerogenic DCs were generated using vitamin D3 and dexamethasone. We added LPS and AVP to the culture medium on day 6 after incubation of DCs at 37 °C. Finally, we assessed the surface molecules by flow cytometry and used real-time PCR to evaluate the expression of genes related to the inhibitory immune checkpoints. Based on the obtained data, AVP increased the expression of CD11c (P ≤ 0.0001), HLA-DR (P ≤ 0.01), and CD86 (P ≤ 0.01) in AVP-mDCs. Also, the expression of all the immune checkpoint genes including CTLA-4 (P ≤ 0.001), BTLA (P ≤ 0.001), PDL-1 (P ≤ 0.05), B7H7 (P ≤ 0.001), LAG3 (P ≤ 0.01), and VISTA (P ≤ 0.001) in AVP-mDCs was increased in comparison to the control group. Vasopressin caused the generation of mature and tolerogenic DCs. Our data may help to consider AVP-mDCs to take part in autoimmune disease therapy, transplanted tissue rejection impedance, and allergies.
精氨酸加压素（AVP）通过包括树突状细胞（DCs）在内的细胞上不同的受体对免疫反应产生不同的影响。本研究旨在探讨AVP对耐受性单核细胞来源的DCs中抑制性免疫检查点分子成熟和表达的影响。采用磁珠分选法（MACS），利用CD14标记从外周血单核细胞（PBMCs）中分离单核细胞。为了将单核细胞分化为DCs，我们使用了粒细胞-巨噬细胞集落刺激因子（GM-CSF）和白细胞介素-4（IL-4）细胞因子。使用维生素D3和地塞米松生成耐受性DCs。在DCs于37℃孵育6天后，我们向培养基中添加脂多糖（LPS）和AVP。最后，我们通过流式细胞术评估表面分子，并使用实时聚合酶链反应（PCR）评估与抑制性免疫检查点相关基因的表达。基于获得的数据，AVP增加了AVP处理的DCs（AVP-mDCs）中CD11c（P≤0.0001）、人类白细胞抗原DR（HLA-DR，P≤0.01）和CD86（P≤0.01）的表达。此外，与对照组相比，AVP-mDCs中所有免疫检查点基因包括细胞毒性T淋巴细胞相关蛋白4（CTLA-4，P≤0.001）、B和T淋巴细胞衰减蛋白（BTLA，P≤0.001）、程序性死亡受体1配体（PDL-1，P≤0.05）、B7同源体7（B7H7，P≤0.001）、淋巴细胞激活基因3（LAG3，P≤0.01）和V域免疫球蛋白抑制T细胞激活（VISTA，P≤0.001）的表达均增加。加压素导致成熟且耐受性DCs的生成。我们的数据可能有助于考虑将AVP-mDCs用于自身免疫性疾病治疗、移植组织排斥反应的阻抗以及过敏反应。
