Cotransfer of antigen and contextual information harmonizes peripheral and lymph node conventional dendritic cell activation.
Cotransfer of antigen and contextual information harmonizes peripheral and lymph node conventional dendritic cell activation.
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抗原和背景信息的共同转移协调外周和淋巴结常规树突状细胞激活。
DOI：
10.1126/sciimmunol.adg8249
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发表时间：
2023
影响因子：
24.8
通讯作者：
Pirillo C
中科院分区：
文献类型：
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作者：
Pirillo C
针对感染和癌症的T细胞反应是由远离攻击部位的淋巴结中的传统树突状细胞（cDC）指导的。从组织行进到淋巴结的迁移性cDC不仅驱动初始T细胞活化，而且将抗原转移到淋巴结驻留的cDC。这些常驻细胞具有定义所产生的T细胞应答的特征的重要作用;然而，鉴于它们的空间分离，它们如何能够适当地加工和呈递抗原以适当地指导应答是未知的。在这里，使用一种新的甲型流感病毒株和一种改良的黑色素瘤模型，我们表明组织和淋巴结cDC激活是协调的，这是由上下文线索的共同转移驱动的。在肿瘤中，肿瘤微环境中的不完全cDC活化由淋巴结驻留的cDC反映，而在流感感染期间，与抗原共转移的病原体相关分子模式驱动驻留cDC中的TLR信号传导及其随后的稳健活化。这种共转移机制解释了个体抗原如何被驻留的cDC不同地处理，以及驱动不良肿瘤cDC活化的信号如何进一步影响淋巴结。我们的研究结果阐明了组织环境如何决定淋巴结中的抗原和T细胞的命运。
T cell responses against infections and cancer are directed by conventional dendritic cells (cDCs) in lymph nodes distant from the site of challenge. Migratory cDCs, which travel from the tissue to the lymph node, not only drive initial T cell activation but also transfer antigen to lymph node–resident cDCs. These resident cells have essential roles defining the character of the resulting T cell response; however, it is unknown how they can appropriately process and present antigens to suitably direct responses given their spatial separation. Here, using a novel strain of influenza A and a modified melanoma model, we show that tissue and lymph node cDC activation is harmonized and that this is driven by cotransfer of contextual cues. In the tumor, incomplete cDC activation in the tumor microenvironment is mirrored by lymph node–resident cDCs, whereas during influenza infection, pathogen-associated molecular patterns cotransferred with antigen drive TLR signaling in resident cDCs and their subsequent robust activation. This cotransfer mechanism explains how individual antigens can be handled distinctly by resident cDCs and how signals driving poor tumoral cDC activation further impact the lymph node. Our findings clarify how tissue context dictates antigenic and, consequently, T cell fate in the lymph node.