心理应激对CD11b~+Gr1~+髓系细胞表型与功能的影响
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摘要
目的探讨心理应激对小鼠CD11b~+Gr1~+髓系细胞表型与功能的影响。方法小鼠束缚心理应激,流式细胞术分析CD11b~+Gr1~+髓系细胞的比例和绝对数,ELISA分析骨髓源CD11b~+Gr1~+细胞与巨噬细胞共培养后IL-6/TNF-α的水平。磁珠分选脾CD4~+CD25-T细胞与纯化Gr1~+细胞共培养检测T细胞增殖能力。结果慢性束缚心理应激导致小鼠骨髓中CD11b~+Gr1~+细胞的子聚集,细胞亚群主要为Ly6G~+Ly6Clow的不成熟中性粒细胞,抑制了脂多糖(LPS)诱导下巨噬细胞产生IL-6/TNF-α,并抑制了T细胞的增殖。结论慢性束缚心理应激诱导小鼠CD11b~+Gr1~+髓系细胞的聚集,对体内免疫细胞发挥抑制作用。
Objective To explore effect of psychological stress on phenotype and function of CD11 b~+Gr1~+myeloid cell in mice. Methods The proportion and absolute numbers of CD11 b~+Gr1~+cells was detected by FACs after chronic restraint pyschological stress. Levels of inflammatory cytokine IL-6/TNF-α secreted by macrophage after co-culture with CD11 b~+Gr1~+were analyzed by ELISA. Splenic CD4~+CD25-T cell was purified by magnisium beads and labeled with CFSE for detection of proliferation activity. Results Chronic psychological stress led to accumulation of CD11 b~+Gr1~+cells in bone marrow of BALB/c mice. A majority accumulated CD11 b~+Gr1~+cells were Ly6 G~+Ly6 Clowimmature neutrophils,which inhibited cytokine release of macrophages and T cell responsiveness. Conclusion Chronic psychological stress induces CD11 b~+Gr1~+myeloid cell accumulation in mice,which can suppress immune cell response.
Objective To explore effect of psychological stress on phenotype and function of CD11 b~+Gr1~+myeloid cell in mice. Methods The proportion and absolute numbers of CD11 b~+Gr1~+cells was detected by FACs after chronic restraint pyschological stress. Levels of inflammatory cytokine IL-6/TNF-α secreted by macrophage after co-culture with CD11 b~+Gr1~+were analyzed by ELISA. Splenic CD4~+CD25-T cell was purified by magnisium beads and labeled with CFSE for detection of proliferation activity. Results Chronic psychological stress led to accumulation of CD11 b~+Gr1~+cells in bone marrow of BALB/c mice. A majority accumulated CD11 b~+Gr1~+cells were Ly6 G~+Ly6 Clowimmature neutrophils,which inhibited cytokine release of macrophages and T cell responsiveness. Conclusion Chronic psychological stress induces CD11 b~+Gr1~+myeloid cell accumulation in mice,which can suppress immune cell response.
引文
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[15] Deng Q,Chen H,Liu Y,et al. Psychological stress promotes neutrophil infiltration in colon tissue through adrenergic signaling in DSS induced colitis model[J]. Brain Behav Immun,2016,57:243-254.
[16] Hiles SA,Baker AL,de Malmanche T,et al. A meta-analysis of differences in IL-6 and IL-10 between people with and without depression:exploring the causes of heterogeneity[J]. Brain Behav Immun,2012,26(7):1180-1188.
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[18] Mundy-Bosse BL,Thornton LM,Yang HC,et al. Psychological stress is associated with altered levels of myeloid derived suppressor cells in breast cancer patients[J]. Cell Immunol,2011,270(1):80-87.
[19] Dowlati Y,Herrmann N,Swardfager W,et al. A meta-analysisof cytokines in major depression[J]. Biol Psychiatry,2010,67(5):446-457.
[20] Li Y,Xiao B,Qiu W,et al. Altered expression of CD4(+)CD25(+)regulatory T cells and its 5-HT(1a)receptor in patients withmajor depression disorder[J]. J Affect Disord,2010,124(1-2):68-75.
[21] Dhabhar FS,McE wen BS. Acute stress enhances while chronic stress suppresses immune function in vivo:a potential role for leukocyte trafficking[J]. Brain Behav Immun,1997,11(4):286-306.
[22] Gabrilovich DI,Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system[J]. Nat Rev Immunol,2009,9(3):162-174.
[23] Sica A,Bronte V. Altered macrophage differentiation and immune dysfunction in tumor development[J]. J Clin Invest,2007,117(5):1155-1166.
[24] Myint AM,Leonard BE,Steinbusch HW,et al. Th1,Th2,and Th3 cytokine alterations in major depression[J]. J Affect Disord,2005,88(2):167-173.
[25] Evans DL,Folds JD,Petitto JM,et al. Circulating natural killer cell phenotypes in men and women with major depression. Relation to cytotoxic activity and severity of depression[J]. Arch Gen Psychiatry,1992,49(5):388-395.
[26] Miller AH. Depression and immunity:a role for T cells[J]?Brain Behav Immun,2010,24(1):1-8.
[2] Kronfol Z,Silva J Jr,Greden J,et al. Impaired lymphocyte function in depressive illness[J]. Life Sci,1983,33(3):241-247.
[3] Lin H,Chen C,Chen BD. Resistance of bone marrow-derived macrophages to apoptosis is associated with the expression of Xlinkedinhibitor of apoptosis protein in primary cultures of bone marrow cells[J]. Biochem J,2001,353(Pt 2):299-306.
[4] Reiche EM,Nunes SO,Morimoto HK. Stress,depression,the immune system,and cancer[J]. Lancet Oncol,2004,5(10):617-625.
[5] Gabrilovich DI,Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system[J]. Nat Rev Immunol,2009,9(3):162-174.
[6] Ostrand-Rosenberg S,Sinha P. Myeloid-derived suppressor cells:linking inflammation and cancer[J]. J Immunol,2009,182(8):4499-4506.
[7] Tacke RS,Lee HC,Goh C,et al. Myeloid suppressor cells induced by hepatitis C virus suppress T-cell responses through the production of reactive oxygen species[J]. Hepatology,2012,55(2):343-353.
[8] Cripps JG,Gorham JD. MDSC in autoimmunity[J]. Int Immunopharmacol,2011,11(7):789-793.
[9] Ioannou M,Alissafi T,Lazaridis I,et al. Crucial role of granulocytic myeloid-derived suppressor cells in the regulation of central nervous system autoimmune disease[J]. J Immunol,2012,188(3):1136-1146.
[10] Obermajer N,Wong JL,Edwards RP,et al. PGE(2)-driven induction and maintenance of cancer-associated myeloid-derived suppressorcells[J]. Immunol Invest,2012,41(6-7):635-57.
[11] Freeman ML,Sheridan BS,Bonneau RH,et al. Psychological stress compromises CD8+T cells control of latent herpes simplex virus type 1 infections[J]. J Immunol,2007,179(1):322-328.
[12] Hunzeker J,Padgett DA,Sheridan PA,et al. Modulation of natural killer cell activity by restraint stress during an influenza A/PR8 infection in mice[J]. Brain Behav Immun,2004,18(6):526-535.
[13] Thaker PH,Han LY,Kamat AA,et al. Chronic stress promotes tumnor growth and angiogenesis in a mouse model of ovarian carcinoma[J]. Nat Med,2006,12(8):939-944.
[14] Heidt T,Sager HB,Courties G,et al. Chronic variable stress activates hematopoietic stem cells[J]. Nat Med,2014,20(7):754-758.
[15] Deng Q,Chen H,Liu Y,et al. Psychological stress promotes neutrophil infiltration in colon tissue through adrenergic signaling in DSS induced colitis model[J]. Brain Behav Immun,2016,57:243-254.
[16] Hiles SA,Baker AL,de Malmanche T,et al. A meta-analysis of differences in IL-6 and IL-10 between people with and without depression:exploring the causes of heterogeneity[J]. Brain Behav Immun,2012,26(7):1180-1188.
[17] Zhao L,Xu J,Liang F,et al. Effect of chronic psychological stress on liver metastasis of colon cancer in mice[J]. PLoSOne,2015,10(10):e0139978.
[18] Mundy-Bosse BL,Thornton LM,Yang HC,et al. Psychological stress is associated with altered levels of myeloid derived suppressor cells in breast cancer patients[J]. Cell Immunol,2011,270(1):80-87.
[19] Dowlati Y,Herrmann N,Swardfager W,et al. A meta-analysisof cytokines in major depression[J]. Biol Psychiatry,2010,67(5):446-457.
[20] Li Y,Xiao B,Qiu W,et al. Altered expression of CD4(+)CD25(+)regulatory T cells and its 5-HT(1a)receptor in patients withmajor depression disorder[J]. J Affect Disord,2010,124(1-2):68-75.
[21] Dhabhar FS,McE wen BS. Acute stress enhances while chronic stress suppresses immune function in vivo:a potential role for leukocyte trafficking[J]. Brain Behav Immun,1997,11(4):286-306.
[22] Gabrilovich DI,Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system[J]. Nat Rev Immunol,2009,9(3):162-174.
[23] Sica A,Bronte V. Altered macrophage differentiation and immune dysfunction in tumor development[J]. J Clin Invest,2007,117(5):1155-1166.
[24] Myint AM,Leonard BE,Steinbusch HW,et al. Th1,Th2,and Th3 cytokine alterations in major depression[J]. J Affect Disord,2005,88(2):167-173.
[25] Evans DL,Folds JD,Petitto JM,et al. Circulating natural killer cell phenotypes in men and women with major depression. Relation to cytotoxic activity and severity of depression[J]. Arch Gen Psychiatry,1992,49(5):388-395.
[26] Miller AH. Depression and immunity:a role for T cells[J]?Brain Behav Immun,2010,24(1):1-8.