Pulmonary Center, Boston University School of Medicine, Boston, MA, 02118, USA.
Department of Microbiology, Boston University School of Medicine, Boston, MA, 02118, USA.
Nat Commun. 2021 Oct 5;12(1):5834. doi: 10.1038/s41467-021-26045-w.
Barrier tissues are populated by functionally plastic CD4 resident memory T (T) cells. Whether the barrier epithelium regulates CD4 T cell locations, plasticity and activities remains unclear. Here we report that lung epithelial cells, including distinct surfactant protein C (SPC)MHC epithelial cells, function as anatomically-segregated and temporally-dynamic antigen presenting cells. In vivo ablation of lung epithelial MHC-II results in altered localization of CD4 T cells. Recurrent encounters with cognate antigen in the absence of epithelial MHC-II leads CD4 T cells to co-express several classically antagonistic lineage-defining transcription factors, changes their cytokine profiles, and results in dysregulated barrier immunity. In addition, lung epithelial MHC-II is needed for surface expression of PD-L1, which engages its ligand PD-1 to constrain lung CD4 T cell phenotypes. Thus, we establish epithelial antigen presentation as a critical regulator of CD4 T cell function and identify epithelial-CD4 T cell immune interactions as core elements of barrier immunity.
屏障组织中存在功能可塑性的 CD4 固有记忆 T（T）细胞。屏障上皮细胞是否调节 CD4 T 细胞的位置、可塑性和活性尚不清楚。在这里，我们报告肺上皮细胞，包括不同的表面活性蛋白 C（SPC）MHC 上皮细胞，作为解剖分离和时间动态的抗原呈递细胞。体内敲除肺上皮细胞 MHC-II 会导致 CD4 T 细胞定位改变。在没有上皮细胞 MHC-II 的情况下，反复接触同源抗原会导致 CD4 T 细胞共表达几种经典拮抗的谱系定义转录因子，改变其细胞因子谱，并导致屏障免疫失调。此外，肺上皮细胞 MHC-II 对于 PD-L1 的表面表达是必需的，PD-L1 与其配体 PD-1 结合以限制肺 CD4 T 细胞表型。因此，我们确立了上皮细胞抗原呈递作为 CD4 T 细胞功能的关键调节剂，并确定上皮细胞-CD4 T 细胞免疫相互作用是屏障免疫的核心要素。
