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.