The nasal-associated lymphoid tissues (NALTs) are mucosal-associated lymphoid organs embedded in the submucosa of the nasal passage. NALTs represent a known site for the deposition of inhaled antigens, but little is known of the mechanisms involved in the induction of immunity within this lymphoid tissue. We find that during the steady state, conventional dendritic cells (cDCs) within the NALTs suppress T cell responses. These cDCs, which are also prevalent within human NALTs (tonsils/adenoids), express a unique transcriptional profile and inhibit T cell proliferation via contact-independent mechanisms that can be diminished by blocking the actions of reactive oxygen species and prostaglandin E₂. Although the prevention of unrestrained immune activation to inhaled antigens appears to be the default function of NALT cDCs, inflammation after localized virus infection recruited monocyte-derived DCs (moDCs) to this region, which diluted out the suppressive DC pool, and permitted local T cell priming. Accommodating for inflammation-induced temporal changes in NALT DC composition and function, we developed an intranasal vaccine delivery system that coupled the recruitment of moDCs with the sustained release of antigen into the NALTs, and we were able to substantially improve T cell responses after intranasal immunization. Thus, homeostasis and immunity to inhaled antigens is tuned by inflammatory signals that regulate the balance between conventional and moDC populations within the NALTs.

鼻相关淋巴组织 (NALT) 是嵌入鼻道黏膜下层的黏膜相关淋巴器官。NALTs 代表了吸入抗原沉积的已知位点，但对在这种淋巴组织内诱导免疫所涉及的机制知之甚少。我们发现，在稳态期间，NALT 中的常规树突状细胞 (cDC) 会抑制 T 细胞反应。这些 cDC 在人类 NALT（扁桃体/腺样体）中也很普遍，它们表达独特的转录特征并通过非接触性机制抑制 T 细胞增殖，这种机制可以通过阻断活性氧和前列腺素 E ₂的作用来减弱. 虽然阻止对吸入抗原的无限制免疫激活似乎是 NALT cDCs 的默认功能，但局部病毒感染后的炎症会将单核细胞衍生的 DCs (moDCs) 募集到该区域，这稀释了抑制性 DC 池，并允许局部 T 细胞启动。为了适应炎症引起的 NALT DC 组成和功能的时间变化，我们开发了一种鼻内疫苗递送系统，该系统将 moDC 的募集与抗原持续释放到 NALT 中相结合，并且我们能够在鼻内免疫后显着改善 T 细胞反应. 因此，体内平衡和对吸入抗原的免疫是通过调节 NALT 内常规和 moDC 群体之间的平衡的炎症信号来调节的。