Induction and activation of human Th17 by targeting antigens to dendritic cells via dectin-1.
Induction and activation of human Th17 by targeting antigens to dendritic cells via dectin-1.
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DOI：
10.4049/jimmunol.1301661
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发表时间：
2014-06-15
期刊：
影响因子：
--
通讯作者：
Oh S
中科院分区：
文献类型：
--
作者：
Duluc D;Joo H;Ni L;Yin W;Upchurch K;Li D;Xue Y;Klucar P;Zurawski S;Zurawski G;Oh S
最近令人信服的证据表明，Th 17赋予宿主针对多种微生物的免疫力，包括细胞外和细胞内病原体。因此，了解抗原特异性Th 17的诱导和激活机制对于合理设计针对病原体的疫苗非常重要。为了研究这一点，我们采用了一种体外系统，其中使用抗hDectin-1-HA 1重组融合蛋白通过Dectin-1将流感HA 1递送至树突状细胞（DC）。我们发现，健康个体维持广泛的HA 1特异性记忆Th 17，其被抗hDectin-1-HA 1靶向的DC有效激活。尽管如此，即使在Th 17促进细胞因子IL-1β和IL-6的存在下，这些DC也不能诱导显著水平的HA 1特异性Th 17应答。我们进一步发现，通过TCR和常见γ链受体的信号诱导表面IL-1 R1表达对于幼稚CD 4 + T细胞分化为HA 1特异性Th 17是必需的。这一过程依赖于MyD 88，而不是IRAK 1/4。因此，STAT 3或MyD 88信号传导的中断导致HA 1特异性Th 17诱导的显著减少。总之，病原体特异性人Th 17的从头产生需要多种信号的复杂但互补的作用。本研究的数据将帮助我们设计新的有效疫苗策略，可以促进Th 17介导的针对微生物病原体的免疫力。
Recent compelling evidence indicates that Th17 confer host immunity against a variety of microbes, including extracellular and intracellular pathogens. Therefore, understanding mechanisms for the induction and activation of antigen-specific Th17 is important for the rational design of vaccines against pathogens. To study this, we employed an in vitro system in which influenza HA1 was delivered to dendritic cells (DCs) via Dectin-1 using anti-hDectin-1-HA1 recombinant fusion proteins. We found that healthy individuals maintained broad ranges of HA1-specific memory Th17 that were efficiently activated by DCs targeted with anti-hDectin-1-HA1. Nonetheless, these DCs were not able to induce significant level of HA1-specific Th17 response even in the presence of Th17-promoting cytokines, IL-1β and IL-6. We further found that the induction of surface IL-1R1 expression by signals via TCRs and common γ-chain receptors were essential for naïve CD4+ T cell differentiation into HA1-specific Th17. This process was dependent on MyD88, but not IRAK1/4. Thus, interruptions in STAT3 or MyD88 signaling led to substantially diminished HA1-specific Th17 induction. Taken together, the de novo generation of pathogen-specific human Th17 requires complex but complementary actions of multiple signals. Data from this study will help us design new and effective vaccine strategy that can promote Th17-mediated immunity against microbial pathogens.
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DOI：
10.1084/jem.20070663
发表时间：
2007-08-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Annunziato F;Cosmi L;Santarlasci V;Maggi L;Liotta F;Mazzinghi B;Parente E;Filì L;Ferri S;Frosali F;Giudici F;Romagnani P;Parronchi P;Tonelli F;Maggi E;Romagnani S
通讯作者：
Romagnani S
影响因子：
30.5
作者：
Acosta-Rodriguez, Eva V.;Napolitani, Giorgio;Sallusto, Federica
通讯作者：
Sallusto, Federica
人白细胞介素17产生的细胞起源于CD161+ CD4+ T细胞前体。
影响因子：
15.3
作者：
Cosmi, Lorenzo;De Palma, Raffaele;Santarlasci, Veronica;Maggi, Laura;Capone, Manuela;Frosali, Francesca;Rodolico, Gabriella;Querci, Valentina;Abbate, Gianfranco;Angeli, Roberta;Berrino, Liberato;Fambrini, Massimiliano;Caproni, Marzia;Tonelli, Francesco;Lazzeri, Elena;Parronchi, Paola;Liotta, Francesco;Maggi, Enrico;Romagnani, Sergio;Annunziato, Francesco
通讯作者：
Annunziato, Francesco
DOI：
10.1038/nri2569
发表时间：
2009-07
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Geijtenbeek TB;Gringhuis SI
通讯作者：
Gringhuis SI
影响因子：
64.8
作者：
Esplugues, Enric;Huber, Samuel;Gagliani, Nicola;Hauser, Anja E.;Town, Terrence;Wan, Yisong Y.;O'Connor, William, Jr.;Rongvaux, Anthony;Van Rooijen, Nico;Haberman, Ann M.;Iwakura, Yoichiro;Kuchroo, Vijay K.;Kolls, Jay K.;Bluestone, Jeffrey A.;Herold, Kevan C.;Flavell, Richard A.
通讯作者：
Flavell, Richard A.