Department of Neonatology, University Children's Hospital, Tuebingen, Germany.
Pediatr Res. 2021 Nov;90(5):989-997. doi: 10.1038/s41390-020-01275-8. Epub 2021 Feb 9.
Neonatal sepsis is a leading cause of neonatal morbidity and mortality, associated with immunosuppression. Myeloid-derived suppressor cells (MDSCs) are cells with immunosuppressive activity, present in high amounts in cord blood. Mechanisms regulating MDSC expansion are incompletely understood. Adenosine is a metabolite with immunoregulatory effects that are elevated in cord blood.
Impact of adenosine on peripheral and cord blood mononuclear cells (PBMCs and CBMCs) was analysed by quantification of ectonucleotidases and adenosine receptor expression, MDSC induction from PBMCs and CBMCs, their suppressive capacity on T cell proliferation and effector enzyme expression by flow cytometry.
Cord blood monocytes mainly expressed CD39, while cord blood T cells expressed CD73. Adenosine-induced MDSCs from PBMCs induced indoleamine-2,3-dioxygenase (IDO) expression and enhanced arginase I expression in monocytes. Concerted action of IDO and ArgI led to effective inhibition of T cell proliferation. In addition, adenosine upregulated inhibitory A receptors on monocytes.
Adenosine acts by inducing MDSCs and upregulating inhibitory A receptors, probably as a mode of autoregulation. Thus, adenosine contributes to immunosuppressive status and may be a target for immunomodulation during pre- and postnatal development.
Immune effector cells, that is, monocytes, T cells and MDSCs from cord blood express ectonucleotidases CD39 and CD73 and may thus serve as a source for adenosine as an immunomodulatory metabolite. Adenosine mediates its immunomodulatory properties in cord blood by inducing MDSCs, and by modulating the inhibitory adenosine A receptor on monocytes. Adenosine upregulates expression of IDO in MDSCs and monocytes potentially contributing to their suppressive activity.
新生儿败血症是导致新生儿发病率和死亡率的主要原因，与免疫抑制有关。髓系来源的抑制细胞（MDSC）是具有免疫抑制活性的细胞，在脐血中大量存在。调节 MDSC 扩增的机制尚不完全清楚。腺苷是一种具有免疫调节作用的代谢物，在脐血中的含量升高。
通过定量分析外核苷酸酶和腺苷受体表达、从 PBMC 和 CBMC 诱导 MDSC、流式细胞术分析其对 T 细胞增殖和效应酶表达的抑制能力，分析腺苷对 PBMC 和 CBMC 的影响。
脐血单核细胞主要表达 CD39，而脐血 T 细胞表达 CD73。腺苷诱导 PBMC 产生的 MDSC 诱导吲哚胺 2,3-双加氧酶（IDO）表达，并增强单核细胞中精氨酸酶 I 的表达。IDO 和 ArgI 的协同作用导致 T 细胞增殖的有效抑制。此外，腺苷上调单核细胞上的抑制性 A 受体。
腺苷通过诱导 MDSC 和上调抑制性 A 受体起作用，可能是一种自身调节方式。因此，腺苷有助于免疫抑制状态，并可能成为产前和产后发育中免疫调节的靶点。
来自脐血的免疫效应细胞，即单核细胞、T 细胞和 MDSC，表达外核苷酸酶 CD39 和 CD73，因此可能是作为免疫调节代谢物腺苷的来源。腺苷通过诱导 MDSC 并调节单核细胞上的抑制性腺苷 A 受体，在脐血中发挥其免疫调节作用。腺苷上调 MDSC 和单核细胞中 IDO 的表达，可能有助于其抑制活性。
