The upper respiratory tract is highly exposed to airborne pathogens and serves as an important inductive site for protective antibody responses, including mucosal IgA and systemic IgG. However, it is currently unknown to what extent inhaled environmental toxins, such as a cigarette smoke, affect the ability to induce antibody-mediated immunity at this site. Using a murine model of intranasal lipopolysaccharide and ovalbumin (LPS/OVA) immunization, we show that cigarette smoke exposure compromises the induction of antigen-specific IgA in the upper airways and systemic circulation. Deficits in OVA-IgA were observed in conjunction with a reduced accumulation of OVA-specific IgA antibody-secreting cells (ASCs) in the nasal mucosa, inductive tissues (NALT, cervical lymph nodes, spleen) and the blood. Nasal OVA-IgA from smoke-exposed mice also demonstrated reduced avidity during the acute post-immunization period in association with an enhanced mutational burden in the cognate nasal Igha repertoire. Mechanistically, smoke exposure attenuated the ability of the nasal mucosa to upregulate VCAM-1 and pIgR, suggesting that cigarette smoke may inhibit both nasal ASC homing and IgA transepithelial transport. Overall, these findings demonstrate the immunosuppressive nature of tobacco smoke and illustrate the diversity of mechanisms through which this noxious stimulus can interfere with IgA-mediated immunity in the upper airways.

上呼吸道高度暴露于空气传播的病原体，是保护性抗体反应的重要诱导部位，包括粘膜 IgA 和全身 IgG。然而，目前尚不清楚吸入的环境毒素（例如香烟烟雾）在多大程度上影响在该部位诱导抗体介导的免疫力的能力。使用鼻内脂多糖和卵清蛋白 (LPS/OVA) 免疫的小鼠模型，我们表明香烟烟雾暴露会损害上呼吸道和体循环中抗原特异性 IgA 的诱导。OVA-IgA 缺陷与 OVA 特异性 IgA 抗体分泌细胞 (ASC) 在鼻粘膜、诱导组织（NALT、颈部淋巴结、脾脏）和血液中的积累减少有关。伊加剧目。从机制上讲，烟雾暴露减弱了鼻粘膜上调 VCAM-1 和 pIgR 的能力，表明香烟烟雾可能抑制鼻 ASC 归巢和 IgA 跨上皮转运。总的来说，这些发现证明了烟草烟雾的免疫抑制性质，并说明了这种有害刺激可以干扰上呼吸道 IgA 介导的免疫的机制的多样性。