SIRPα is a transmembrane protein that binds the protein tyrosine phosphatases SHP-1 and SHP-2 through its cytoplasmic region and is abundantly expressed on monocytes, dendritic cells, and macrophages. Studies recently showed that SIRPα is essential for priming of CD4 + T cells by DCs and for development of Th17 cell-mediated autoimmune diseases. We have now further evaluated the importance of SIRPα and that of its ligand CD47 in primary immune thrombocytopenia (ITP). In this study, we show that there was a low expression state of SIRPα on the surface of monocytes. Treatment of cells culture from ITP patients with a mAb to SIRPα that blocks the binding of SIRPα to CD47 downregulated the ITP response. The abilities of monocytes from ITP patients to stimulate an allogenic MLR were reduced. The proliferation of, and production of IL-2, by CD4 + T cells from ITP patients were inhibited, the Treg cell numbers and the production of IL-10 pairs were upregulated, and the production of TGF-β not was inhibited, by a mAb to SIRPα. Moreover, a mAb to SIRPα, the expression of HLA-DR and CD86 were markedly inhibited and the expression of CD80 was slightly upregulated, on the surface of CD14 + monocytes from ITP patients as compared with healthy subjects. However, blockade of SIRPα increased the secretion of TLR-dependent cytokines TNF-α, IL-6 and IL-1β by PBMCs, which may be considered as a reserve in response to danger signals. These results suggest that SIRPα on monocytes is essential for the priming of naive T cells and the development of ITP. Therefore, SIRPα is a potential therapeutic target for ITP and other autoimmune diseases.

SIRPα 是一种跨膜蛋白，通过其细胞质区域结合蛋白酪氨酸磷酸酶 SHP-1 和 SHP-2，并在单核细胞、树突细胞和巨噬细胞上大量表达。最近的研究表明，SIRPα 对于 DC 启动 CD4 + T 细胞以及 Th17 细胞介导的自身免疫性疾病的发展至关重要。我们现在进一步评估了 SIRPα 及其配体 CD47 在原发性免疫性血小板减少症 (ITP) 中的重要性。在本研究中，我们发现单核细胞表面存在 SIRPα 的低表达状态。使用 SIRPα 单克隆抗体治疗 ITP 患者的细胞培养物，阻断 SIRPα 与 CD47 的结合，从而下调 ITP 反应。ITP 患者的单核细胞刺激同种异体 MLR 的能力降低。ITP 患者的 CD4 + T 细胞的增殖和 IL-2 的产生受到抑制，Treg 细胞数量和 IL-10 对的产生上调，并且 TGF-β 的产生不受抑制。 SIRPα 的单克隆抗体。此外，与健康受试者相比，针对SIRPα的mAb，ITP患者的CD14+单核细胞表面的HLA-DR和CD86的表达被显着抑制，CD80的表达略微上调。然而，阻断SIRPα会增加PBMCs分泌TLR依赖性细胞因子TNF-α、IL-6和IL-1β，这可能被认为是响应危险信号的储备。这些结果表明单核细胞上的 SIRPα 对于初始 T 细胞的启动和 ITP 的发展至关重要。因此，SIRPα是ITP和其他自身免疫性疾病的潜在治疗靶点。