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Effects of myeloid-derived suppressor cells induced by dexamethasone on rejection of skin transplantation of mice

LIAO Jiong-bo1, SHAO Kun1, WANG Xiao2, LIU Guang-wei2, XU Da1, ZHOU Pei-jun1, WANG Xiang-hui1   

  1. 1.Renal Transplantation Center， Ruijin Hospital， Shanghai Jiao Tong University School of Medicine， Shanghai 200025， China； 2.Department of Immunology， School of Basic Medical Sciences， Fudan University， Shanghai 200032， China
  • Online:2014-06-28 Published:2014-06-30
  • Supported by:

    Foundation of International Communication and Cooperation of the Ministry of Health of China，IHECC07-001； Research Project of Key Laboratory of Organ Transplantation of Science and Technology Commission of Shanghai Municipality，10DZ2212000

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Abstract:

Objective To investigate the expression and immunoregulation effect of myeloid-derived suppressor cells (MDSCs) induced by dexamethasone in the skin transplantation model of mice. Methods The male C57BL/6 mice were receptors and the female BALB/c mice were donors. The tailback skin transplantation model of mice was then established (n=40). Donor mice were randomly divided into the experiment group and control group (n=20). Mice of the experiment group received an intraperitoneal injection of dexamethasone 5 mg/kg per day while mice of the control group received an equal volume of saline. The rejection of skin allograft was observed and the rejection time was determined. The transplanted skin was excised for pathological examination on the seventh day after operations. Some mice were sacrificed on the ninth day after operations and their spleens and draining lymph nodes of transplanted skin were obtained and detected by the flow cytometry. Results The median survival time of allograft skin of the experiment group was (24±3.062) days, significantly longer than (9±0.816) days of the control group (P<0.05). HE stained paraffin sections showed that the rejection of skin graft of the experiment group was significantly less serious than that of the control group. The results of the flow cytometry indicated that in spleen tissues of the experiment group, the proportion of CD11b+GR1+ cells was significantly higher than that of the control group, the expression of TNF-α was down-regulated (P<0.05), the expression of IL-10 was up-regulated (P<0.05), and expressions of chemotactic factor receptor CXCR2 and adhesion molecules CD44 and CD62L were increased (P<0.05). In the draining lymph nodes of the experiment group, the proportion of CD11b+GR1+ cells was significantly higher than that of the control group (P<0.05), while the proportion of CD4+T cells and the expression of IFN-γ were significantly decreased (P<0.05). Conclusion Dexamethasone may induce the MDSCs and promote MDSCs migrate to the allograft region. By inhibiting the function of CD4+T cells, MDSCs can relieve the graft rejection and extend the survival time of grafts.

Key words: myeloid-derived suppressor cells, dexamethasone, skin transplantation, immunoregulation, mice