Distinct alterations of CD68+CD163+ M2-like macrophages and myeloid-derived suppressor cells in newly diagnosed primary immune thrombocytopenia with or without CR after high-dose dexamethasone treatment

Xia Shao; Boting Wu; Luya Cheng; Feng Li; Yanxia Zhan; Chanjuan Liu; Lili Ji; Zhihui Min; Yang Ke; Lihua Sun; Hao Chen; Yunfeng Cheng

doi:10.1186/s12967-018-1424-8

Distinct alterations of CD68⁺CD163⁺ M2-like macrophages and myeloid-derived suppressor cells in newly diagnosed primary immune thrombocytopenia with or without CR after high-dose dexamethasone treatment

J Transl Med. 2018 Mar 2;16(1):48. doi: 10.1186/s12967-018-1424-8.

Authors

Xia Shao¹, Boting Wu², Luya Cheng¹, Feng Li^{1

3}, Yanxia Zhan¹, Chanjuan Liu¹, Lili Ji¹, Zhihui Min^{4

5}, Yang Ke¹, Lihua Sun³, Hao Chen⁶, Yunfeng Cheng^{7

8

9

10}

Affiliations

¹ Department of Hematology, Zhongshan Hospital Fudan University, Shanghai, 200032, China.
² Department of Transfusion Medicine, Zhongshan Hospital Fudan University, Shanghai, 200032, China.
³ Department of Hematology, Zhongshan Hospital Qingpu Branch, Fudan University, Shanghai, 201700, China.
⁴ Institute of Clinical Science, Department of Hematology, Zhongshan Hospital, Fudan University, 180 Fenglin Rd, Shanghai, 200032, China.
⁵ Shanghai Institute of Clinical Bioinformatics, Fudan University Center for Clinical Bioinformatics, Shanghai, 200032, China.
⁶ Department of Thoracic Surgery, Zhongshan Hospital Qingpu Branch, Fudan University, Shanghai, 201700, China.
⁷ Department of Hematology, Zhongshan Hospital Fudan University, Shanghai, 200032, China. yfcheng@fudan.edu.cn.
⁸ Department of Hematology, Zhongshan Hospital Qingpu Branch, Fudan University, Shanghai, 201700, China. yfcheng@fudan.edu.cn.
⁹ Institute of Clinical Science, Department of Hematology, Zhongshan Hospital, Fudan University, 180 Fenglin Rd, Shanghai, 200032, China. yfcheng@fudan.edu.cn.
¹⁰ Shanghai Institute of Clinical Bioinformatics, Fudan University Center for Clinical Bioinformatics, Shanghai, 200032, China. yfcheng@fudan.edu.cn.

Abstract

Background: Although impaired myeloid-derived suppressor cells (MDSCs) recently have been studied in immune thrombocytopenia (ITP), another myeloid-derived cell population signified as M2 macrophages has not been investigated properly in ITP patients. 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: Peripheral blood mononuclear cells from healthy controls and primary ITP patients were isolated to test the circulating M2-like macrophages and MDSCs. The circulating M2-like macrophage population defined as CD68⁺CD163⁺ and circulating MDSC population as CD11b⁺CD33⁺HLA-DR^- were determined by flow cytometry. Plasma inflammatory cytokines were measured by multiplex ELISA.

Results: The percentages of MDSCs were found to be expanded in newly diagnosed patients of ITP, especially among those of the complete response (CR) group (p < 0.0001). Positive linear correlation was verified between percentages of M2-like macrophages and MDSCs. The same correlation was also determined in the CR group. After treatment, the percentages of M2-like macrophages and MDSCs were both increased significantly in CR group, while those patients among the PR + NR group manifested a significant numeric decrease of MDSCs but only a moderate decrease in M2-like macrophages. MIP-1α/CCL3 was negatively correlated with M2-like macrophages while MCP-1 possessed a positive correlation with M2-like macrophages, eotaxin-1/CCL11 was negatively correlated with MDSCs and interleukin-1β (IL-1β) was found to be negatively correlated with both M2-like macrophages and MDSCs.

Conclusions: The present findings indicated critical roles of both circulating M2-like macrophages and MDSCs in ITP. The positive correlation between them might be related to inflammatory factors-mediated bidirectional interactions or partially due to their similar background patterns during differentiation. MIP-1α/CCL3, MCP-1, eotaxin-1/CCL11 and IL-1β might play a critical role in the expansion of both M2 macrophages and MDSCs population in ITP patients, which deserves further investigation.

Keywords: Dexamethasone; Immune thrombocytopenia; M2-like macrophages; MDSCs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Antigens, CD / metabolism*
Antigens, Differentiation, Myelomonocytic / metabolism*
CD163 Antigen
Cell Proliferation / drug effects
Cytokines / blood
Dexamethasone / pharmacology
Dexamethasone / therapeutic use*
Female
Humans
Macrophages / drug effects
Macrophages / metabolism*
Male
Middle Aged
Myeloid-Derived Suppressor Cells / metabolism*
Purpura, Thrombocytopenic, Idiopathic / blood
Purpura, Thrombocytopenic, Idiopathic / diagnosis*
Purpura, Thrombocytopenic, Idiopathic / drug therapy*
Purpura, Thrombocytopenic, Idiopathic / immunology
Receptors, Cell Surface / metabolism*
Treatment Outcome

Substances

Antigens, CD
Antigens, Differentiation, Myelomonocytic
CD163 Antigen
CD68 antigen, human
Cytokines
Receptors, Cell Surface
Dexamethasone

Abstract

Publication types

MeSH terms

Substances

Grants and funding