Department of Discovery Immunology, Genentech, South San Francisco, CA.
Department of OMNI Bioinformatics, Genentech, South San Francisco, CA.
J Immunol. 2023 Sep 1;211(5):844-852. doi: 10.4049/jimmunol.2200946.
The lung is a barrier tissue with constant exposure to the inhaled environment. Therefore, innate immunity against particulates and pathogens is of critical importance to maintain tissue homeostasis. Although the lung harbors both myelinating and nonmyelinating Schwann cells (NMSCs), NMSCs represent the most abundant Schwann cell (SC) population in the lung. However, their contribution to lung physiology remains largely unknown. In this study, we used the human glial fibrillary acidic protein promoter driving tdTomato expression in mice to identify SCs in the peripheral nervous system and determine their location within the lung. Single-cell transcriptomic analysis revealed the existence of two NMSC populations (NMSC1 and NMSC2) that may participate in pathogen recognition. We demonstrated that these pulmonary SCs produce chemokines and cytokines upon LPS stimulation using in vitro conditions. Furthermore, we challenged mouse lungs with LPS and found that NMSC1 exhibits an enriched proinflammatory response among all SC subtypes. Collectively, these findings define the molecular profiles of lung SCs and suggest a potential role for NMSCs in lung inflammation.
肺是一种具有屏障功能的组织，其组织细胞会持续暴露于吸入的环境中。因此，先天免疫系统对于颗粒物和病原体的防御对于维持组织内环境稳定至关重要。尽管肺中存在髓鞘形成 Schwann 细胞（MNSCs）和非髓鞘形成 Schwann 细胞（NMSCs），但 NMSCs 是肺中最丰富的 Schwann 细胞群体。然而，它们在肺生理学中的作用在很大程度上尚不清楚。在这项研究中，我们使用人类胶质纤维酸性蛋白启动子驱动小鼠中的 tdTomato 表达，以鉴定周围神经系统中的 Schwann 细胞，并确定它们在肺中的位置。单细胞转录组分析揭示了两种 NMSC 群体（NMSC1 和 NMSC2）的存在，它们可能参与病原体的识别。我们使用体外条件证明了这些肺 Schwann 细胞在 LPS 刺激下会产生趋化因子和细胞因子。此外，我们用 LPS 对小鼠肺部进行了挑战，发现所有 Schwann 细胞亚型中，NMSC1 表现出更强烈的促炎反应。总之，这些发现定义了肺 Schwann 细胞的分子特征，并提示 NMSCs 在肺炎症中可能发挥作用。
