Ectopic Lymphoid Follicle Formation and Human Seasonal Influenza Vaccination Responses Recapitulated in an Organ-on-a-Chip.
Ectopic Lymphoid Follicle Formation and Human Seasonal Influenza Vaccination Responses Recapitulated in an Organ-on-a-Chip.
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DOI：
10.1002/advs.202103241
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发表时间：
2022-05
期刊：
影响因子：
15.1
通讯作者：
Ingber, Donald E.
中科院分区：
文献类型：
--
作者：
Goyal, Girija;Prabhala, Pranav;Mahajan, Gautam;Bausk, Bruce;Gilboa, Tal;Xie, Liangxia;Zhai, Yunhao;Lazarovits, Roey;Mansour, Adam;Kim, Min Sun;Patil, Aditya;Curran, Danielle;Long, Jaclyn M.;Sharma, Sanjay;Junaid, Abidemi;Cohen, Limor;Ferrante, Thomas C.;Levy, Oren;Prantil-Baun, Rachelle;Walt, David R.;Ingber, Donald E.
淋巴滤泡（LFs）在次级淋巴器官中负责产生适应性免疫反应，并在慢性炎症期间异位形成。异位LF形成的人类模型将为了解LF的发展提供工具，并为疫苗的临床前评估提供非人类灵长类动物的替代方法。本研究表明，在双通道器官芯片微流控装置的一个通道内，在3D细胞外基质凝胶中培养，人血液中的原代B淋巴细胞和T淋巴细胞可自主组装成异位LFs。通过微孔膜分离的平行通道的超融合是LF形成所必需的，并阻止淋巴细胞自激活。这些生发中心样LFs含有表达激活诱导胞苷脱氨酶的B细胞，并在激活后表现出浆细胞分化。为了探索它们在季节性疫苗测试中的效用，将自体单核细胞来源的树突状细胞整合到LF芯片中。与2D培养物相比，人LF芯片对分裂病毒粒子流感疫苗的抗体反应更好，2D培养物被角鲨烯乳液佐剂增强，这伴随着LF大小和数量的增加。当接种商业流感疫苗时，观察到浆细胞的形成和抗血凝素IgG的产生，以及在临床相关时间尺度上与接种疫苗的人相似的细胞因子的分泌。从血液中提取的原代人淋巴细胞通过器官芯片装置的灌注重新编程为淋巴滤泡（LF）。这些异位LFs表达AID，在不同刺激物（包括佐剂和季节性流感疫苗）的激活下，可诱导形成浆细胞和抗原特异性抗体。
Lymphoid follicles (LFs) are responsible for generation of adaptive immune responses in secondary lymphoid organs and form ectopically during chronic inflammation. A human model of ectopic LF formation will provide a tool to understand LF development and an alternative to non‐human primates for preclinical evaluation of vaccines. Here, it is shown that primary human blood B‐ and T‐lymphocytes autonomously assemble into ectopic LFs when cultured in a 3D extracellular matrix gel within one channel of a two‐channel organ‐on‐a‐chip microfluidic device. Superfusion via a parallel channel separated by a microporous membrane is required for LF formation and prevents lymphocyte autoactivation. These germinal center‐like LFs contain B cells expressing Activation‐Induced Cytidine Deaminase and exhibit plasma cell differentiation upon activation. To explore their utility for seasonal vaccine testing, autologous monocyte‐derived dendritic cells are integrated into LF Chips. The human LF chips demonstrate improved antibody responses to split virion influenza vaccination compared to 2D cultures, which are enhanced by a squalene‐in‐water emulsion adjuvant, and this is accompanied by increases in LF size and number. When inoculated with commercial influenza vaccine, plasma cell formation and production of anti‐hemagglutinin IgG are observed, as well as secretion of cytokines similar to vaccinated humans over clinically relevant timescales. Primary human lymphocytes taken from blood are reprogrammed into lymphoid follicles (LF) by superfusion in an organ chip device. These ectopic LFs express AID and can be induced to form plasma cells and antigen‐specific antibodies upon activation with different stimuli including adjuvants and seasonal influenza vaccines.
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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
树突状细胞对于维持流感病毒感染小鼠肺部的三级淋巴结构至关重要。
DOI：
10.1084/jem.20090410
发表时间：
2009-10-26
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
GeurtsvanKessel CH;Willart MA;Bergen IM;van Rijt LS;Muskens F;Elewaut D;Osterhaus AD;Hendriks R;Rimmelzwaan GF;Lambrecht BN
通讯作者：
Lambrecht BN
影响因子：
20.3
作者：
Huggins, Jennifer;Pellegrin, Tina;Zand, Martin S.
通讯作者：
Zand, Martin S.
影响因子：
1.7
作者：
Byers, Anthony M.;Tapia, Tenekua M.;Wittman, Vaughan
通讯作者：
Wittman, Vaughan
影响因子：
64.8
作者：
Cabrita, Rita;Lauss, Martin;Jonsson, Goran
通讯作者：
Jonsson, Goran