免疫抑制与单核细胞亚群
Immunosuppression and monocyte subsets.
作者信息
Rogacev Kyrill S, Zawada Adam M, Hundsdorfer Johanna, Achenbach Marina, Held Gerhard, Fliser Danilo, Heine Gunnar H
机构信息
Department of Internal Medicine IV, Saarland University Medical Center, Homburg, Germany Department of Internal Medicine III, Saarland University Medical Center, Homburg, Germany.
Department of Internal Medicine IV, Saarland University Medical Center, Homburg, Germany.
出版信息
Nephrol Dial Transplant. 2015 Jan;30(1):143-53. doi: 10.1093/ndt/gfu315. Epub 2014 Oct 13.
BACKGROUND
Monocytes are critical in innate immunity and transplantation. Three monocyte subsets exist, CD14(++)CD16(-), CD14(++)CD16(+) and CD14(+)CD16(++) monocytes; cell counts of CD14(++)CD16(+) and CD14(+)CD16(++) monocytes are increased in pre-transplant chronic kidney disease. Interestingly, the effect of immunosuppressants on monocyte heterogeneity has not been well studied.
METHODS
The impact of immunosuppressants on monocyte subsets was studied: (i) in 152 kidney transplant (KTx) recipients to characterize subset distribution in the steady state, (ii) in patients after autologous (n = 10) versus allogenic (n = 9) haematopoietic stem cell transplantation (HSCT) to analyse monocyte subset development and (iii) in an in vitro model to compare the effect of immunosuppressants on monocyte subset biology.
RESULTS
In KTx, steroid intake was associated with higher total, CD14(++)CD16(-) and CD14(++)CD16(+) monocyte counts, but fewer CD14(+)CD16(++) monocytes, whereas intake of mycophenolate, calcineurin inhibitors (CNI) and mammalian target of rapamycin inhibitors (mTORI) did not affect monocyte (subset) counts. In linear regression analysis, only steroid intake was a significant determinant of monocyte (subset) counts: total monocytes (β = 0.331; P < 0.001), CD14(++)CD16(-) monocytes (β = 0.374; P < 0.001), CD14(++)CD16(+) monocytes (β = 0.221; P = 0.010) and CD14(+)CD16(++) monocytes (β = -0.169; P = 0.049). After HSCT, CD14(++)CD16(-) monocytes were the first to arise, followed by CD14(++)CD16(+) and later by CD14(+)CD16(++) monocytes. Monocyte subset distribution did not differ significantly in patients after allogenic compared with autologous transplantation. CNI, mycophenolate and methotrexate did not influence monocyte subset development, but modified surface receptor expression (CCR2, HLA-DR, ENG, TEK and TLR4) in allogenic HSCT.
CONCLUSION
Chronic low-dose steroids are associated with monocytosis and higher counts of CD14(++)CD16(-) and of proinflammatory CD14(++)CD16(+) monocytes.
背景
单核细胞在固有免疫和移植中起关键作用。存在三种单核细胞亚群，即CD14(++)CD16(-)、CD14(++)CD16(+)和CD14(+)CD16(++)单核细胞；移植前慢性肾脏病患者中CD14(++)CD16(+)和CD14(+)CD16(++)单核细胞的细胞计数增加。有趣的是，免疫抑制剂对单核细胞异质性的影响尚未得到充分研究。
方法
研究了免疫抑制剂对单核细胞亚群的影响：(i) 在152例肾移植（KTx）受者中，以表征稳态下的亚群分布；(ii) 在自体（n = 10）与异体（n = 9）造血干细胞移植（HSCT）后的患者中，分析单核细胞亚群的发育情况；(iii) 在体外模型中，比较免疫抑制剂对单核细胞亚群生物学特性的影响。
结果
在肾移植受者中，服用类固醇与总单核细胞、CD14(++)CD16(-)和CD14(++)CD16(+)单核细胞计数较高相关，但CD14(+)CD16(++)单核细胞较少，而霉酚酸酯、钙调神经磷酸酶抑制剂（CNI）和雷帕霉素靶蛋白抑制剂（mTORI）的服用不影响单核细胞（亚群）计数。在线性回归分析中，只有类固醇服用是单核细胞（亚群）计数的显著决定因素：总单核细胞（β = 0.331；P < 0.001）、CD14(++)CD16(-)单核细胞（β = 0.374；P < 0.001）、CD14(++)CD16(+)单核细胞（β = 0.221；P = 0.010）和CD14(+)CD16(++)单核细胞（β = -0.169；P = 0.049）。造血干细胞移植后，CD14(++)CD16(-)单核细胞最先出现，其次是CD14(++)CD16(+)单核细胞，随后是CD14(+)CD16(++)单核细胞。与自体移植后的患者相比，异体移植患者的单核细胞亚群分布无显著差异。CNI、霉酚酸酯和甲氨蝶呤不影响单核细胞亚群的发育，但改变了异体造血干细胞移植中表面受体的表达（CCR2、HLA-DR、ENG、TEK和TLR4）。
结论
慢性低剂量类固醇与单核细胞增多以及CD14(++)CD16(-)和促炎性CD14(++)CD16(+)单核细胞计数增加有关。
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