靶向树突状细胞的脓毒症免疫调理新策略

姚咏明; 张卉; 吴瑶

doi:10.3760/cma.j.cn501225-20230321-00087

靶向树突状细胞的脓毒症免疫调理新策略

doi: 10.3760/cma.j.cn501225-20230321-00087

解放军总医院医学创新研究部转化医学研究中心、第四医学中心，北京　　100853

基金项目:

国家重点研发计划 2022YFA1104604

国家自然科学基金重点项目 82130062, 82241062

详细信息

通讯作者:
姚咏明，Email：c_ff@sina.com

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- 被引次数: 0
出版历程
- 收稿日期: 2023-03-21

Novel strategy of sepsis immunomodulation targeting dendritic cells

Translational Medicine Research Center, Medical Innovation Research Division and the Fourth Medical Center of PLA General Hospital, Beijing 100853, China

Funds:

National Key Research and Development Program of China 2022YFA1104604

Key Program of National Natural Science Foundation of China 82130062, 82241062

More Information

Corresponding author: Yao Yongming, Email: c_ff@sina.com

摘要

摘要: 树突状细胞是介导机体天然免疫和获得性免疫应答的主要抗原提呈细胞。脓毒症状态下，树突状细胞数目减少，抗原提呈能力减弱，分泌细胞因子异常，造成T淋巴细胞活化障碍。既往研究提示，树突状细胞数目和功能变化是导致免疫功能抑制的主要原因之一。笔者针对脓毒症时树突状细胞的变化特点，结合其目前的研究进展，简要分析并提出了靶向树突状细胞凋亡、分化和功能等方面的免疫调理新策略，以期为严重烧创伤并发脓毒症的有效防治提供新思路。
- 脓毒症 /
- 免疫，细胞 /
- 树突细胞 /
- 免疫反应 /
- 免疫调理 /
- 干预策略
Abstract: Dendritic cells (DCs) are the major antigen-presenting cells that play critical roles in regulating both innate and acquire immune responses. In the state of sepsis, the number of DCs is obviously decreased with inhibited antigen presenting ability as well as abnormal cytokine secretion, thereby resulting in an impairment of T lymphocyte activation. Previous studies have demonstrated that the depletion and dysfunction of DCs appear to be the main causes associated with the development of sepsis-induced immunosuppression. Based on the characteristic changes of DCs in sepsis and analysis of recent research progress, the authors propose a novel strategy of immunomodulation targeting the apoptosis, differentiation, and dysfunction of DCs, in order to provide new ideas for the prevention and treatment of severe burns and trauma complicated with sepsis.
- Sepsis /
- Immunity, cellular /
- Dendritic cells /
- Immune response /
- Immunomodulation /
- Interference strategy
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参考文献(35)

[1]	RuddKE, JohnsonSC, AgesaKM, et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study[J]. Lancet, 2020,395(10219):200-211. DOI: 10.1016/S0140-6736(19)32989-7.
[2]	LiuJ, ZhangX, ChengY, et al. Dendritic cell migration in inflammation and immunity[J]. Cell Mol Immunol, 2021,18(11):2461-2471. DOI: 10.1038/s41423-021-00726-4.
[3]	曾茁, 彭毅志, 袁志强. 脓毒症生物标志物的研究进展[J]. 中华烧伤与创面修复杂志, 2023, 39(7): 679-684. DOI: 10.3760/cma.j.cn501225-20230320-00086.
[4]	VolkHD, ReinkeP, KrauschD, et al. Monocyte deactivation--rationale for a new therapeutic strategy in sepsis[J]. Intensive Care Med, 1996,22 Suppl 4:S474-481. DOI: 10.1007/BF01743727.
[5]	WuDD, LiT, JiXY. Dendritic cells in sepsis: pathological alterations and therapeutic implications[J]. J Immunol Res, 2017, 2017:3591248. DOI: 10.1155/2017/3591248.
[6]	PèneF, CourtineE, OuaazF, et al. Toll-like receptors 2 and 4 contribute to sepsis-induced depletion of spleen dendritic cells[J]. Infect Immun, 2009,77(12):5651-5658. DOI: 10.1128/IAI.00238-09.
[7]	GautierEL, HubyT, Saint-CharlesF, et al. Enhanced dendritic cell survival attenuates lipopolysaccharide-induced immunosuppression and increases resistance to lethal endotoxic shock[J]. J Immunol, 2008,180(10):6941-6946. DOI: 10.4049/jimmunol.180.10.6941.
[8]	CremerI, Dieu-NosjeanMC, MaréchalS, et al. Long-lived immature dendritic cells mediated by TRANCE-RANK interaction[J]. Blood, 2002,100(10):3646-3655. DOI: 10.1182/blood-2002-01-0312.
[9]	WongBR, JosienR, LeeSY, et al. TRANCE (tumor necrosis factor [TNF]-related activation-induced cytokine), a new TNF family member predominantly expressed in T cells, is a dendritic cell-specific survival factor[J]. J Exp Med, 1997,186(12):2075-2080. DOI: 10.1084/jem.186.12.2075.
[10]	Ricaño-PonceI, RizaAL, de NooijerAH, et al. Characterization of sepsis inflammatory endotypes using circulatory proteins in patients with severe infection: a prospective cohort study[J]. BMC Infect Dis, 2022,22(1):778. DOI: 10.1186/s12879-022-07761-0.
[11]	WangLX, RenC, YaoRQ, et al. Sestrin2 protects against lethal sepsis by suppressing the pyroptosis of dendritic cells[J]. Cell Mol Life Sci, 2021,78(24):8209-8227. DOI: 10.1007/s00018-021-03970-z.
[12]	LiJY, RenC, WangLX, et al. Sestrin2 protects dendrite cells against ferroptosis induced by sepsis[J]. Cell Death Dis, 2021,12(9):834. DOI: 10.1038/s41419-021-04122-8.
[13]	FrenckRW, SarmanG, HarperTE, et al. The ability of recombinant murine granulocyte-macrophage colony-stimulating factor to protect neonatal rats from septic death due to Staphylococcus aureus[J]. J Infect Dis, 1990,162(1):109-114. DOI: 10.1093/infdis/162.1.109.
[14]	BoL, WangF, ZhuJ, et al. Granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) for sepsis: a meta-analysis[J]. Crit Care, 2011,15(1):R58. DOI: 10.1186/cc10031.
[15]	MeiselC, SchefoldJC, PschowskiR, et al. Granulocyte-macrophage colony-stimulating factor to reverse sepsis-associated immunosuppression: a double-blind, randomized, placebo-controlled multicenter trial[J]. Am J Respir Crit Care Med, 2009,180(7):640-648. DOI: 10.1164/rccm.200903-0363OC.
[16]	DonnenbergVS, O'ConnellPJ, LogarAJ, et al. Rare-event analysis of circulating human dendritic cell subsets and their presumptive mouse counterparts[J]. Transplantation, 2001,72(12):1946-1951. DOI: 10.1097/00007890-200112270-00014.
[17]	AnandasabapathyN, BretonG, HurleyA, et al. Efficacy and safety of CDX-301, recombinant human Flt3L, at expanding dendritic cells and hematopoietic stem cells in healthy human volunteers[J]. Bone Marrow Transplant, 2015,50(7):924-930. DOI: 10.1038/bmt.2015.74.
[18]	PatilNK, BohannonJK, LuanL, et al. Flt3 ligand treatment attenuates T cell dysfunction and improves survival in a murine model of burn wound sepsis[J]. Shock, 2017, 47(1):40-51. DOI: 10.1097/SHK.0000000000000688.
[19]	HundeshagenG, CuiW, MusgroveL, et al. Fms-like tyrosine kinase-3 ligand attenuates local and systemic infection in a model of post-burn pneumonia[J]. Shock, 2018, 49(6):721-727. DOI: 10.1097/SHK.0000000000000964.
[20]	BhardwajN, FriedlanderPA, PavlickAC, et al. Flt3 ligand augments immune responses to anti-DEC-205-NY-ESO-1 vaccine through expansion of dendritic cell subsets[J]. Nat Cancer, 2020,1(12):1204-1217. DOI: 10.1038/s43018-020-00143-y.
[21]	OberholzerA, OberholzerC, EfronPA, et al. Functional modification of dendritic cells with recombinant adenovirus encoding interleukin 10 for the treatment of sepsis[J]. Shock, 2005,23(6):507-515.
[22]	ZhuXM, YaoYM, LiangHP, et al. The effect of high mobility group box-1 protein on splenic dendritic cell maturation in rats[J]. J Interferon Cytokine Res, 2009,29(10):677-686. DOI: 10.1089/jir.2008.0104.
[23]	徐姗, 姚咏明, 董宁, 等. 高迁移率族蛋白B1对大鼠脾脏树突状细胞表面共刺激分子表达的影响[J].中华创伤杂志,2006,22(8):579-583. DOI: 10.3760/j:issn:1001-8050.2006.08.005.
[24]	NakosG, Malamou-MitsiVD, LachanaA, et al. Immunoparalysis in patients with severe trauma and the effect of inhaled interferon-gamma[J]. Crit Care Med, 2002,30(7):1488-1494. DOI: 10.1097/00003246-200207000-00015.
[25]	PayenD, FaivreV, MiatelloJ, et al. Multicentric experience with interferon gamma therapy in sepsis induced immunosuppression: a case series[J]. BMC Infect Dis, 2019, 19(1):931. DOI: 10.1186/s12879-019-4526-x.
[26]	LeentjensJ, KoxM, KochRM, et al. Reversal of immunoparalysis in humans in vivo: a double-blind, placebo-controlled, randomized pilot study[J]. Am J Respir Crit Care Med, 2012,186(9):838-845. DOI: 10.1164/rccm.201204-0645OC.
[27]	ShaoR, FangY, YuH, et al. Monocyte programmed death ligand-1 expression after 3-4 days of sepsis is associated with risk stratification and mortality in septic patients: a prospective cohort study[J]. Crit Care, 2016,20(1):124. DOI: 10.1186/s13054-016-1301-x.
[28]	ChangK, SvabekC, Vazquez-GuillametC, et al. Targeting the programmed cell death 1: programmed cell death ligand 1 pathway reverses T cell exhaustion in patients with sepsis[J]. Crit Care, 2014,18(1):R3. DOI: 10.1186/cc13176.
[29]	HotchkissRS, ColstonE, YendeS, et al. Immune checkpoint inhibition in sepsis: a Phase 1b randomized study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of nivolumab[J]. Intensive Care Med, 2019,45(10):1360-1371. DOI: 10.1007/s00134-019-05704-z.
[30]	HotchkissRS, ColstonE, YendeS, et al. Immune checkpoint inhibition in sepsis: a phase 1b randomized, placebo-controlled, single ascending dose study of antiprogrammed cell death-ligand 1 antibody (BMS-936559) [J]. Crit Care Med, 2019, 47(5):632-642. DOI: 10.1097/CCM.0000000000003685.
[31]	WangWD, YangXR, GuoMF, et al. Up-regulation of BTLA expression in myeloid dendritic cells associated with the treatment outcome of neonatal sepsis[J]. Mol Immunol, 2021,134:129-140. DOI: 10.1016/j.molimm.2021.03.007.
[32]	ChengT, BaiJ, ChungCS, et al. Enhanced innate inflammation induced by anti-BTLA antibody in dual insult model of hemorrhagic shock/sepsis[J]. Shock, 2016, 45(1):40-49. DOI: 10.1097/SHK.0000000000000479.
[33]	BenjamimCF, LundySK, LukacsNW, et al. Reversal of long-term sepsis-induced immunosuppression by dendritic cells[J]. Blood, 2005,105(9):3588-3595. DOI: 10.1182/blood-2004-08-3251.
[34]	WangHW, YangW, GaoL, et al. Adoptive transfer of bone marrow-derived dendritic cells decreases inhibitory and regulatory T-cell differentiation and improves survival in murine polymicrobial sepsis[J]. Immunology, 2015,145(1):50-59. DOI: 10.1111/imm.12423.
[35]	GaoS, ZengL, ZhangX, et al. Attenuated Streptococcus pneumoniae vaccine candidate SPY1 promotes dendritic cell activation and drives a Th1/Th17 response[J]. Immunol Lett, 2016, 179:47-55. DOI: 10.1016/j.imlet.2016.08.008.