Engineered Human Dendritic Cell Exosomes as Effective Delivery System for Immune Modulation.
Engineered Human Dendritic Cell Exosomes as Effective Delivery System for Immune Modulation.
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DOI：
10.3390/ijms241411306
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发表时间：
2023-07-11
影响因子：
5.6
通讯作者：
Cutler, Christopher W.
中科院分区：
文献类型：
--
作者：
Elsayed, Ranya;Elashiry, Mahmoud;Tran, Cathy;Yang, Tigerwin;Carroll, Angelica;Liu, Yutao;Hamrick, Mark;Cutler, Christopher W.
外泌体（exos）含有对癌症和其他炎性疾病具有治疗和诊断价值的分子货物，但其对牙周炎（PD）的治疗潜力仍不清楚。树突状细胞（Dendritic cells，DCs）是免疫应答的指挥者，已广泛应用于免疫治疗。我们先前在PD小鼠模型中报道，定制的小鼠DC衍生的exo亚型可以根据免疫特征将免疫应答重新编程为骨保留或骨丢失表型。这项技术的进一步发展需要用人类靶细胞测试基于DC的人类exos。我们在这项研究中的主要目的是测试的假设，人单核细胞来源的树突状细胞（MoDC）衍生的exos构成了一个良好的耐受性和有效的免疫治疗方法，以调节人靶DC和T细胞的免疫反应在体外。用TGF β/IL-10产生MoDC亚型（调节性（reg）MoDC，CD 86 lowHLA-DRlowPDL 1high），E. coli LPS（刺激性（stim）MoDCs，CD 86 highHLA-DRhighPDL 1 low）和缓冲液（未成熟（i）MoDCs，CD 86 lowHLA-DRmedPDL 1 low）。从不同的MoDC亚型中分离外来体并进行表征。一旦从分泌细胞释放到周围环境中，外泌体就会保护其预先包装的分子货物并将其递送到旁观者细胞。这调节这些细胞的功能，取决于货物的内容。RegMoDCexos被受体MoDC内化并诱导PDL 1上调和共刺激分子CD 86、HLADR和CD 80下调，而stimMoDCexos具有相反的影响。RegMoDCexos诱导CD 25 + Foxp 3 + T细胞亚群，其表达CTLA 4和PD 1，但不表达IL-17 A。相反，用stimMoDCexos处理的T细胞诱导IL-17 A + Th 17 T细胞，其对免疫调节CTLA 4和PD 1呈阴性。用iMoDCexos处理的T细胞和DC是免疫“中性”的，相当于对照。总之，人DC exos提供了一种有效的递送系统来调节体外人DC和T细胞免疫应答。因此，MoDC exos可能是一种可行的免疫调节剂，用于调节牙龈组织中的免疫反应，以抑制牙周病中的骨丢失。
Exosomes (exos) contain molecular cargo of therapeutic and diagnostic value for cancers and other inflammatory diseases, but their therapeutic potential for periodontitis (PD) remains unclear. Dendritic cells (DCs) are the directors of immune response and have been extensively used in immune therapy. We previously reported in a mouse model of PD that custom murine DC-derived exo subtypes could reprogram the immune response toward a bone-sparing or bone-loss phenotype, depending on immune profile. Further advancement of this technology requires the testing of human DC-based exos with human target cells. Our main objective in this study is to test the hypothesis that human monocyte-derived dendritic cell (MoDC)-derived exos constitute a well-tolerated and effective immune therapeutic approach to modulate human target DC and T cell immune responses in vitro. MoDC subtypes were generated with TGFb/IL-10 (regulatory (reg) MoDCs, CD86lowHLA-DRlowPDL1high), E. coli LPS (stimulatory (stim) MoDCs, CD86highHLA-DRhighPDL1low) and buffer (immature (i) MoDCs, CD86lowHLA-DRmedPDL1low). Exosomes were isolated from different MoDC subtypes and characterized. Once released from the secreting cell into the surrounding environment, exosomes protect their prepackaged molecular cargo and deliver it to bystander cells. This modulates the functions of these cells, depending on the cargo content. RegMoDCexos were internalized by recipient MoDCs and induced upregulation of PDL1 and downregulation of costimulatory molecules CD86, HLADR, and CD80, while stimMoDCexos had the opposite influence. RegMoDCexos induced CD25+Foxp3+ Tregs, which expressed CTLA4 and PD1 but not IL-17A. In contrast, T cells treated with stimMoDCexos induced IL-17A+ Th17 T cells, which were negative for immunoregulatory CTLA4 and PD1. T cells and DCs treated with iMoDCexos were immune ‘neutral’, equivalent to controls. In conclusion, human DC exos present an effective delivery system to modulate human DC and T cell immune responses in vitro. Thus, MoDC exos may present a viable immunotherapeutic agent for modulating immune response in the gingival tissue to inhibit bone loss in periodontal disease.
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DOI：
10.1038/mt.2008.1
发表时间：
2008-04
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子：
--
作者：
Dai S;Wei D;Wu Z;Zhou X;Wei X;Huang H;Li G
通讯作者：
Li G
影响因子：
5.2
作者：
Bergomas F;Grizzi F;Doni A;Pesce S;Laghi L;Allavena P;Mantovani A;Marchesi F
通讯作者：
Marchesi F
DOI：
10.1126/science.aau6977
发表时间：
2020-02-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kalluri R;LeBleu VS
通讯作者：
LeBleu VS
影响因子：
4.4
作者：
Benson, Robert A.;Patakas, Agapitos;Brewer, James M.
通讯作者：
Brewer, James M.
影响因子：
7.4
作者：
Morse MA;Garst J;Osada T;Khan S;Hobeika A;Clay TM;Valente N;Shreeniwas R;Sutton MA;Delcayre A;Hsu DH;Le Pecq JB;Lyerly HK
通讯作者：
Lyerly HK