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

// Shasha Zhao 1, 2 , Zhenyang Gu 1 , Li Wang 1, 3 , Lixun Guan 1 , Feiyan Wang 1 , Nan Yang 1 , Lan Luo 1 , Zhe Gao 1 , Yingwei Song 4 , Lili Wang 1 , Daihong Liu 1 and Chunji Gao 1 1 Department of Hematology, Chinese PLA General Hospital, Beijing 100853, China 2 Medical School, Nankai University, Tianjin 300071, China 3 Department of Hematology and Oncology, Laoshan Branch, No. 401 Hospital of Chinese PLA, Qingdao 266101, China 4 Department 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.