Oncotarget

Research Papers:

G-CSF inhibits LFA-1-mediated CD4+ T cell functions by inhibiting Lck and ZAP-70

Shasha Zhao, Zhenyang Gu, Li Wang, Lixun Guan, Feiyan Wang, Nan Yang, Lan Luo, Zhe Gao, Yingwei Song, Lili Wang, Daihong Liu and Chunji Gao _

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Oncotarget. 2017; 8:51578-51590. https://doi.org/10.18632/oncotarget.18194

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Abstract

Shasha Zhao1,2, Zhenyang Gu1, Li Wang1,3, Lixun Guan1, Feiyan Wang1, Nan Yang1, Lan Luo1, Zhe Gao1, Yingwei Song4, Lili Wang1, Daihong Liu1 and Chunji Gao1

1Department of Hematology, Chinese PLA General Hospital, Beijing 100853, China

2Medical School, Nankai University, Tianjin 300071, China

3Department of Hematology and Oncology, Laoshan Branch, No. 401 Hospital of Chinese PLA, Qingdao 266101, China

4Department of Blood Transfusion, Chinese PLA General Hospital, Beijing 100853, China

Correspondence to:

Chunji Gao, email: gaochunji@medmail.com.cn

Keywords: granulocyte colony-stimulating factor, CD4+ T cells, lymphocyte function-associated antigen-1, Lck, ZAP-70

Received: July 26, 2016     Accepted: May 06, 2017     Published: May 25, 2017

ABSTRACT

In this study, we showed that G-CSF mobilization increased the frequency of T cells, specifically CD3+CD4+ T cells. G-CSF mobilization decreased the secretion of inflammatory cytokines of CD4+ T cells through the LFA-1/ICAM-1 signaling pathway, whereas it did not alter the TH1/TH2 ratio. We found that G-CSF mobilization inhibited LFA-1-mediated CD4+ T cell polarization and motility. In vitro, G-CSF stimulation also attenuated the polarization and adhesiveness of CD4+ T cells through the LFA-1/ICAM-1 interaction. Further investigation revealed that G-CSF mobilization suppressed LFA-1 signaling by down-regulating Lck and ZAP-70 expression in CD4+ T cells, similar results was also confirmed by in-vitro studies. These findings suggested that G-CSF directly suppressed LFA-1-mediated CD4+ T cell functions through the down-regulation of Lck and ZAP-70. The immunosuppressive effect of G-CSF mobilization deepened our understanding about peripheral blood hematopoietic stem cell transplantation. LFA-1/ICMA-1 pathway may become a potential target for graft-versus-host disease prophylaxis.


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