Modulation of human Th17 cell responses through complement receptor 3 (CD11 b/CD18) ligation on monocyte-derived dendritic cells.
Modulation of human Th17 cell responses through complement receptor 3 (CD11 b/CD18) ligation on monocyte-derived dendritic cells.
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通过补体受体3（CD11b/CD18）结扎对单核细胞衍生的树突状细胞的补体3（CD11b/CD18）的调节。
DOI：
10.1016/j.jaut.2018.05.005
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发表时间：
2018-08
影响因子：
12.8
通讯作者：
Bhardwaj N
中科院分区：
文献类型：
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作者：
Nowatzky J;Manches O;Khan SA;Godefroy E;Bhardwaj N
凋亡细胞受体通过在凋亡细胞或微粒摄取后调节树突状细胞功能而有助于诱导耐受。已经结合或摄取凋亡细胞的树突状细胞仅产生少量的促炎细胞因子，并且不能引发效应T细胞应答。具体而言，凋亡细胞受体CR 3（CD 11 B/CD 18）在人单核细胞衍生的树突状细胞（moDC）上的连接下调促炎细胞因子分泌，但对人Th 17细胞稳态和效应反应的后果仍然未知。在这里，我们的目的是确定CD 11b连接的moDC是否调节Th 17细胞效应器反应，以评估其未来在基于moDC的抑制性免疫治疗中的应用潜力。我们产生了一个基于珠的替代系统，以靶向CD 11b单核细胞衍生的人树突状细胞和检查的影响，CD 11b连接的Th 17-偏斜细胞因子分泌，引发，扩增和功能可塑性的DC/T细胞共培养系统在多和单克隆水平。我们表明，通过靶向moDC上的CD 11b受体，人记忆CD 4 + T细胞区室中的Th 17细胞扩增被有效地限制。这种致耐受性能力主要依赖于细胞因子偏斜。此外，在rs 11143679（ITGAM）变体的健康纯合子携带者（人类系统性红斑狼疮的强遗传易感性标记）上连接CD 11b也下调了Th 17-偏斜细胞因子的分泌。总的来说，我们的研究结果强调了靶向CD 11b连接人树突状细胞的潜力，用于Th 17相关自身免疫性疾病的抑制性免疫治疗。
Apoptotic cell receptors contribute to the induction of tolerance by modulating dendritic cell function following the uptake of apoptotic cells or microparticles. Dendritic cells that have bound or ingested apoptotic cells produce only low amounts of pro-inflammatory cytokines and fail to prime effector T cell responses. Specifically, ligation of the apoptotic cell receptor CR3 (CD11 b/CD18) on human monocyte-derived dendritic cells (moDC) down-modates proinflammatory cytokine secretion, but the consequences for human Th17 cell homeostasis and effector responses remain unknown. Here, we aimed to establish whether CD11b-ligated moDC modulate Th17 cell effector reponses to assess their potential for future use in moDC-based suppressive immunotherapy. We generated a bead-based surrogate system to target CD11b on monocyte-derived human dendritic cells and examined the effects of CD11b ligation on Th17-skewing cytokine secretion, priming, expansion and functional plasticity in DC/T cell co-culture systems at the poly- and monoclonal level. We show that Th17 cell expansion within the human memory CD4+ T cell compartment was efficiently constricted by targeting the CD11b receptor on moDC. This tolerogenic capacity was primarily dependent on cytokine skewing. Furthermore, ligation of CD11b on healthy homozygous carriers of the rs11143679 (ITGAM) variant – a strong genetic susceptibility marker for human systemic lupus erythematosus – also down-modulated the secretion of Th17-skewing cytokines. Overall, our findings underline the potential of targeted CD11b ligation on human dendritic cells for the engineering of suppressive immunotherapy for Th17-related autoimmune disorders.
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影响因子：
15.3
作者：
Bonifaz, L;Bonnyay, D;Mahnke, K;Rivera, M;Nussenzweig, MC;Steinman, RM
通讯作者：
Steinman, RM
影响因子：
30.5
作者：
Acosta-Rodriguez, Eva V.;Napolitani, Giorgio;Sallusto, Federica
通讯作者：
Sallusto, Federica
影响因子：
20.3
作者：
Kryczek, Ilona;Banerjee, Mousumi;Zou, Weiping
通讯作者：
Zou, Weiping
DOI：
10.4049/jimmunol.0903595
发表时间：
2010-05-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kyttaris VC;Zhang Z;Kuchroo VK;Oukka M;Tsokos GC
通讯作者：
Tsokos GC
影响因子：
30.5
作者：
通讯作者：
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