Division of Protective Immunity, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Nat Commun. 2021 Jun 28;12(1):3993. doi: 10.1038/s41467-021-23619-6.
Type II alveolar cells (AT2s) are critical for basic respiratory homeostasis and tissue repair after lung injury. Prior studies indicate that AT2s also express major histocompatibility complex class II (MHCII) molecules, but how MHCII expression by AT2s is regulated and how it contributes to host defense remain unclear. Here we show that AT2s express high levels of MHCII independent of conventional inflammatory stimuli, and that selective loss of MHCII from AT2s in mice results in modest worsening of respiratory virus disease following influenza and Sendai virus infections. We also find that AT2s exhibit MHCII presentation capacity that is substantially limited compared to professional antigen presenting cells. The combination of constitutive MHCII expression and restrained antigen presentation may position AT2s to contribute to lung adaptive immune responses in a measured fashion, without over-amplifying damaging inflammation.
II 型肺泡细胞（AT2）对于基本呼吸稳态和肺损伤后的组织修复至关重要。先前的研究表明，AT2 也表达主要组织相容性复合体 II 类（MHCII）分子，但 AT2 中 MHCII 的表达如何受到调节以及它如何有助于宿主防御仍不清楚。在这里，我们发现 AT2 在不受常规炎症刺激的情况下表达高水平的 MHCII，并且在小鼠中选择性地从 AT2 中丢失 MHCII 会导致流感和仙台病毒感染后呼吸道病毒疾病的适度恶化。我们还发现 AT2 表现出 MHCII 呈递能力，与专业抗原呈递细胞相比受到极大限制。组成性 MHCII 表达和受限制的抗原呈递的组合可能使 AT2 以适度的方式为肺适应性免疫反应做出贡献，而不会过度放大破坏性炎症。
