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. 2022 Sep 9:13:989230.
doi: 10.3389/fimmu.2022.989230. eCollection 2022.

Effect of Angelica polysaccharide on mouse myeloid-derived suppressor cells

Jie Shen  1 , Mengyu Zhang  1 , Ke Zhang  1 , Yahan Qin  1 , Meifang Liu  2 , Shujuan Liang  2 , Daquan Chen  3 , Meiyu Peng  1   2
Affiliations

Effect of Angelica polysaccharide on mouse myeloid-derived suppressor cells

Jie Shen et al. Front Immunol. .

Abstract

Angelica polysaccharide (APS) is a polysaccharide extracted from Angelica sinensis and it is one of the main active components of Angelica sinensis. Many studies have demonstrated that APS can promote the activation and function of a variety of immune cells and is recognized as an immune enhancer, but the regulatory effect of APS on myeloid-derived suppressor cells (MDSC) is still unclear. In this study, we investigated the effects of APS on MDSC proliferation, differentiation and function through in vivo and in vitro experiments. In vitro, our results showed that APS promoted the proliferation, differentiation and immunosuppressive function of MDSC through STAT1 and STAT3 signaling pathways, and positively correlated with the expression level of Mannose receptor (MR, also known as CD206) and in a concentration-dependent manner on APS. In vivo, APS up-regulated T cells, γδT cells, CD8+T cells, natural killer cells, monocytes/macrophages, and granulocytes in the peripheral blood and spleen of mice to varying degrees and was accompanied by the same degree of increase in the proportion of MDSC. That reminds to the clinician that when applying APS as treatment they should pay attention to its possible side effects of increasing the quantity and function of MDSC, in order to increase its efficacy.

Keywords: Angelica polysaccharide; differentiation; immunosuppression; mannose receptor; myeloid-derived suppressor cells; proliferation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The effect of APS on MDSC proliferation. (A) BMC which were isolated from normal mouse were treated with APS (0, 80, 160 and 320 μg/ml) for 72 h. One representative result from each experiment is shown. (B) Proliferation index of BMC which were isolated from normal mouse treated with APS. (C) BMC which were isolated from normal mouse were treated with GM-CSF and APS (0, 80, 160 and 320 μg/ml) for 72 h. One representative result from each experiment is shown. (D) Proliferation index of MDSC (**p<0.01, *p<0.05). n=5, Data are expressed by mean ± SD.
Figure 2
Figure 2
The effect of APS on MDSC differentiation. BMC which were isolated from normal mouse and were divided into the MR (CD206) high expression group and the MR (CD206) low expression group. Then they were treated with APS (0, 80, 160 and 320 μg/ml) for 96h in the presence of GM-CSF. (A, B) One representative result from each experiment is shown. The percentages of M-MDSC (C), PMN-MDSC (D) and total MDSC (E) among the induced MDSC in vitro (**p<0.01, *p<0.05). n=5, Data are expressed by mean ± SD.
Figure 3
Figure 3
APS increases H2O2, ROS production and the expression of MDSC-associated genes. MDSC were isolated from peripheral blood, spleen and bone marrow from tumor-bearing mice using anti-mouse Ly-6G and Ly-6C particle-DM, then they were treated with APS (0, 80, 160 and 320 μg/ml) for 48h. (A, C) One representative result from each experiment is shown. The H2O2 + cells% (B) and the MFI of the ROS detection (D) in the isolated MDSC (*** p<0.001, ** p<0.01, * p<0.05). The expression of the MDSC associated genes ARG-1 (E) and iNOS (F) was analyzed using qPCR (** p<0.01, * p<0.05). n=5, Data are expressed by mean ± SD.
Figure 4
Figure 4
The effect of APS in spleen index and thymus index on mice. Mice were euthanized after 8 weeks of Control/APS-treated. (A) Final Spleen index (***p<0.001). (B) Final Thymic index. n=6, Data are expressed by mean ± SD.
Figure 5
Figure 5
The percentages of T cells, T subpopulations and B cells in the spleen and peripheral blood. The spleen and peripheral blood were collected from the Control/APS-treated mice. Single-cell suspensions were generated, and the cells were immune-stained for CD3, CD8, CD4 and γδ. (A–E) One representative result from each experiment is shown. The percentages of CD3+ cells among the lymphocytes in spleen (F) and blood (H) (***p<0.001). The percentages of CD3+CD4+T, CD3+CD8+T cells and γδ+T cells among the CD3+T population from lymphocytes in spleen (G) and blood (I) (***p<0.001, *p<0.05).The ratio of T/MDSC in splenocytes (J) and blood (K). The percentages of CD19+ cells among the lymphocytes from splenocytes (L) and blood (M) (*p<0.05). n=6, Data are expressed by mean ± SD.
Figure 6
Figure 6
The percentages of NK cells, granulocytes and monocytes/macrophages in the spleen and peripheral blood. The spleen and peripheral blood were collected from the Control/APS-treated mice. Single-cell suspensions were generated, and the cells were immune-stained for CD19 and NK1.1. (A, D, G) One representative result from each experiment is shown. The percentages of NK1.1+ cells among the lymphocytes from splenocytes (B) and blood (C) (*p<0.05). (E) The percentages of CD11b+Gr1+ cells among the leukocytes in blood (*p<0.05). (F) The ratio of G/MDSC in blood. The percentages of CD11b+F4/80+ cells among the leukocytes in blood (H) and splenocytes (I) (*p<0.05). (J) The ratio of NK/MDSC in blood. (K) The ratio of NK/MDSC in spleen. (L) The ratio of Mo/MDSC in blood. (M) The ratio of Mɸ/MDSC in spleen. n=6, Data are expressed by mean ± SD.
Figure 7
Figure 7
The percentages of Treg and MDSC in spleen and peripheral blood. The spleen and peripheral blood were collected from the Control/APS-treated mice. Single-cell suspensions were generated, and the cells were immune-stained for Treg、M-MDSC、PMN-MDSC and MDSC. (A, D) One representative result from each experiment is shown. The percentages of Treg cells among lymphocytes in spleen (B) and blood (C). The percentages of M-MDSCs and PMN-MDSCs of CD11b+ cells among splenocytes (E) and leukocytes in blood (G) (*p<0.05). The percentages of total MDSC among splenocytes (F) and leukocytes in blood (H) (*p<0.05). n=6, Data are expressed by mean ± SD.
Figure 8
Figure 8
APS up-regulated STAT1 and STAT3 signaling pathways in MDSC. MDSC isolated from tumor-bearing mice were treated with APS at a concentration of 0, 80, 160 and 320 μg/ml for 12 h. (A, C) One representative result from each experiment is shown. (B) The MFI of p-STAT1 in MDSC (***p<0.001, **p<0.01, *p<0.05). (D) The MFI of p-STAT3 in MDSC (***p<0.001). n=6, Data are expressed by mean ± SD.
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