| Objective:Acute pancreatitis(AP)is a local or systemic inflammatory response caused by abnormal pancreatin activation in vivo.Imbalance between proinflammatory immune system and anti-inflammatory immune system is an important mechanism that promotes disease progression.Myeloid-derived suppressor cells(MDSCs)are regulatory immune cells derived from bone marrow,which play inhibitory function through immune suppressive receptors(IRs).However,the changes and roles of MDSC in the AP process have not been reported yet.Interleukin(IL)-37 is a newly discovered anti-inflammatory cytokine,which can exert anti-inflammatory effect by inducing phenotypic transformation of regulatory immune cells,etc.Elevated IL-37 level was found in the plasma of the patients during our preliminary study.In this study,IL-37were analyzed to explain the effect and mechanism of IL-37 on the occurrence and development of functional regulation,so as to provide new ideas for the treatment of patients in vivo and in vitro.Methods:(1)The proportion and number of HLADR~-CD11b~+MDSC and its subsets G-MDSC and M-MDSC(CD66b~+CD14~-granulocytes and CD66b~-CD14~+monocytes)in patients and healthy controls(HC)were determined by Flow Cytometry(FCM),and their correlation with APACHE II score and C-reactive protein were analyzed.The method was used to analyze the difference in cell inhibitory function between the sources of hydroxy fluorescein diacetate succinimide(CFSE)and severe acute pancreatitis(SAP).Analysis was performed to determine whether there was any difference in the expression of Arginase-1,Reactive oxygen species(ROS)and mean fluorescence intensity(MFI)of CD155 from the source.(2)The proportion and number of CD3~+T cells and their subsets CD4~+and CD8~+cells in peripheral blood of patients were analyzed,and also the proportion of IFN-γin these T cells.The relationship among the expression of IFN-γ,cell proliferation and TIGIT on the surface of T cells was also analyzed.(3)Enzyme linked immunosorbent assay(ELISA)was used to detect the plasma IL-37 concentration of HC and patients with AP.The correlation between IL-37concentration and APACHE II score,C-reactive protein and MDSC was analyzed.PBMC treated with IL-37 for 24 hours was detected,MDSC proportion and surface CD155 intensity were analyzed.Furthermore,MDSC treated with IL-37 were co-cultured with T cells,then the proliferation rate was detected.HC and SAP-derived MDSC were co-cultured with TIGIT~+and TIGIT~-cells respectively,then cell proliferation rate in each group was analyzed.Results:(1)The proportion of MDSC cells and their subsets,G-MDSC and M-MDSC,inPBMC of AP patients was increased and positively correlated with APACHE IIscore and CRP.CD3~+T cells were inhibited by MDSC derived from SAP patients.The expression of Arg-1,ROS and CD155 were increased in MDSCs from SAPpatients.(2)The proportion and absolute number of CD3~+,CD4~+and CD8~+T cells in PBMC inAP patients were decreased.Furthermore,IFN-γand TIGIT of T cells wasdecreased in patients with AP.The expression of IFN-γand the cell proliferationability were also increased in TIGIT~+T cells compared with that of TIGIT~-T cells.(3)Plasma IL-37 concentration in AP patients was higher than that in HC,which wasnegatively correlated with MDSC.PBMCs treated with IL-37 in vitro did notchange the proportion of MDSC in PBMC,but with enhanced inhibitory effect ofMDSC.IL-37 decreased the expression of ROS and CD155,but had no effect onthe expression of Arg-1.MDSC inhibited T cell proliferation through theCD155/TIGIT signaling pathway.Conclusions:In this study,we found that MDSC increased in patients with AP,and the inhibitory function of MDSC was enhanced.IL-37 level was increased in plasma in patients with AP.The inhibitory effect of MDSC was enhanced by IL-37.However,the specific mechanism is unclear.This study is about the pathogenesis of AP and provides a new idea for the treatment of SAP by preventing AP progression. |
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