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. 2021 Jan 11:10:585216.
doi: 10.3389/fonc.2020.585216. eCollection 2020.

Increased Circulating of CD54highCD181low Neutrophils in Myelodysplastic Syndrome

Liyan Yang  1 , Hongzhao Li  1 , Yumei Liu  1 , Xinyan Xie  1 , Huiqin Zhang  1 , Haiyue Niu  1 , Zonghong Shao  1 , Limin Xing  1 , Huaquan Wang  1
Affiliations

Increased Circulating of CD54highCD181low Neutrophils in Myelodysplastic Syndrome

Liyan Yang et al. Front Oncol. .

Abstract

Myelodysplastic syndromes (MDSs) are a group of heterogeneous hematopoietic stem/progenitor cells clonal diseases, characteristic features with myeloid dysplasia, leading to abnormality of neutrophils. Recent studied have showed that neutrophils act not only as professional killers, but also as regulators of innate and adaptive immune in infection and inflammatory condition. The CD54highCD181low neutrophils are a kind of reverse-transmigrated neutrophils characterized proinflammatory phenotype. We investigated the frequency and functional properties of circulating CD54highCD181low neutrophils in patients with untreated MDS. Frequency of CD54highCD181low neutrophils was significantly increased in MDS patients and related to the severity of the disease. Furthermore, CD54highCD181low neutrophils suppressed CD8+ T cells functions in vitro. CD54highCD181low neutrophils lead to upregulation of PD1 on CD8+ T cells. Higher CD54highCD181low neutrophils were related to poor prognosis and more infections. The frequency of CD54highCD181low neutrophils decreased in high risk MDS patients who had response after treatment with decitabine. Overall, we identified CD54highCD181low neutrophils expanded in MDS. The exact mechanisms of increased CD54highCD181low neutrophils and its effect on immune function remain to be elucidated.

Keywords: CD181; CD54/ICAM-1; immunity; myelodysplastic syndromes; neutrophils.

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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
Increased frequency of CD54highCD181low neutrophils cells in the peripheral blood of new diagnosis myelodysplastic syndromes (MDS) patients. (A, B) Frequency of peripheral blood neutrophils were compared between 23 healthy controls (HC) and 37 new diagnosis MDS patients. FSC and SSC were used to gate neutrophils. CD33 positive and CD11b positive were used to confirm neutrophils (C++). (C, D) Representative dot plots from flow cytometric (FACS) analyses showing the CD54highCD181low cell frequency among peripheral blood neutrophils obtained from HC (n = 23) and MDS patients (n = 37) (I represents CD54highCD181low neutrophils). (E, F) Mean fluorescence index (MFI) levels of CD54 on the CD33 and CD11b neutrophils was compared between HC (n = 23) and MDS patients (n = 37). The bars represent the standard error of the mean. ***P < 0.001.
Figure 2
Figure 2
Impact of CD54highCD181low neutrophils from myelodysplastic syndromes (MDS) patients on T cells. (A) The dose-dependent suppressive activity of FACS-sorted CD54highCD181low neutrophils from MDS patients (n=6) was evaluated in coculture experiments with autologous T cells activated by means of anti-CD2, -CD3, and -CD28 microbeads. Proliferation of T cells was assessed after 5 days by CCK-8 assay and compared with stimulated T cells alone (set as 100% T-cell proliferation). (B) The levels of lactate dehydrogenase (LDH) in supernatant of coculture experiments with CD54highCD181low neutrophils, CD3+ T cells and effector cells. (C) The perforin of CD3+CD8+ T cells before and after coculture with CD54highCD181low neutrophils from the peripheral blood of MDS patients. (D) The granzyme B of CD3+CD8+ T cells before and after coculture with CD54highCD181low neutrophils from the peripheral blood of MDS patients. The bars represent the standard error of the mean. *P < 0.05; **P < 0.01.
Figure 3
Figure 3
CD54highCD181low neutrophils from myelodysplastic syndromes (MDS) patients (n = 6) lead to upregulation of PD1 expression on CD8+ T cells. The bars represent the standard error of the mean. *P < 0.05.
Figure 4
Figure 4
CD54highCD181low neutrophils are related to the prognosis and infection of myelodysplastic syndromes (MDS) patients. (A) The frequency of CD54highCD181low neutrophils is related with overall survival of MDS patients. P < 0.05 (B) The ratio of acute myeloid leukemia transformation was higher in higher frequency of CD54highCD181low neutrophils group. P<0.05 (C) The incidence of infection was higher in higher frequency of CD54highCD181low neutrophils group at diagnosis time. P < 0.05.
Figure 5
Figure 5
The change of CD54highCD181low neutrophils from myelodysplastic syndromes (MDS) patients at new diagnosis (ND) and post-therapy (PT). (A) Low risk MDS patient (n = 12). P > 0.05. (B) high risk MDS patients without good response (CR+PR) (N = 6). P > 0.05. (C) high risk MDS patients with good response (CR+PR) (N = 4). P < 0.05.
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