CD68⁺ CD163⁺ M2-like Macrophages and Myeloid-Derived Suppressor Cells in Primary Immune Thrombocytopenia

Background

Clinical investigations for the pathogenesis of immune thrombocytopenia (ITP) have focused on the aberrations related to adaptive immunity including platelet autoantibodies, T-cell clonality, and T helper differentiation. Recently, impaired myeloid-derived suppressor cells (MDSCs) have been implicated to participate in the pathogenesis of ITP, which could also act as a prognostic marker for treatment responses. However, another myeloid-derived cell population signified as M2 macrophages, has not been investigated properly in ITP patients. M2 macrophages, predominantly characterized as CD68⁺ (pan macrophages) and CD163⁺ (M2 specific), could promote immune modulation and tissue remodeling. Interestingly, a bidirectional cross-talk has been revealed between M2 macrophages known as "tumor associated macrophages" and MDSCs via high level of IL-10 in tumor microenvironments, which could result in facilitating tumor progression. These immunemodulation properties of MDSCs and M2 macrophages are posited to be severe disadvantages in tumor-bearing patients, while they might be beneficial in autoimmunity. In the present study, we intended to determine the features of circulating M2-like macrophages, to examine its relationship with MDSCs, and to explore their prognostic values in ITP.

Methods

PBMC were isolated from the freshly collected peripheral blood of 10 healthy controls and 28 primary ITP patients. The circulating M2-like macrophages were defined as CD68⁺CD163⁺ (intracellular staining), and the phenotypic features of the circulating MDSCs were CD11b⁺CD33⁺HLA-DR^- (surface staining). Stained cells were tested by FACS Aria II flow cytometer.

Results

There are 17 patients in CR, and 11 patients in NR group. The population of circulating MDSCs expanded in newly diagnosed patients with ITP (p < 0.001), especially among the CR group (p < 0.001), but no significant difference was found in circulating M2-like macrophages. Positive linear correlation was verified between percentages of circulating M2-like macrophages and MDSCs (r= 0.15, p= 0.045). The same correlation was also determined in the CR group (r= 0.30, p= 0.021) while not in the NR group (r= 0.11, p= 0.313). Compared with those before the treatment, the percentages of both M2-like macrophages (p = 0.039) and MDSCs (p = 0.036) increased significantly after the treatment among patients in CR group, however, decreased number of MDSCs was found in NR group patients (p = 0.035).

Conclusions

The present investigation indicated critical roles of both circulating M2-like macrophages and MDSCs in the pathogenesis of ITP. The positive correlation between them might be related to some bidirectional interaction or partially due to their similar background patterns during differentiation. Further studies are required to demonstrate the cytokine profile related to the expansion of both MDSCs and M2 macrophages population in ITP patients.