Institute of Molecular Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074, Aachen, Germany.
Center for Translational Immunology, UMC Utrecht, Utrecht, The Netherlands.
Sci Rep. 2023 Jan 27;13(1):1509. doi: 10.1038/s41598-023-28554-8.
Macrophages are traditionally considered antigen-presenting cells. However, their ability to present antigen and the factors regulating macrophage MHCII expression are poorly understood. Here, we demonstrate that MHCII expression on murine intestinal macrophages is differentially controlled by their residence in the small intestine (SI) or the colon, their ontogeny and the gut microbiota. Monocyte-derived macrophages are uniformly MHCII, independently of the tissue of residence, microbial status or the age of the mouse, suggesting a common monocyte differentiation pathway. In contrast, MHCII expression on long-lived, prenatally-derived Tim4 macrophages is low after birth but significantly increases at weaning in both SI and colon. Furthermore, MHCII expression on colonic Tim4, but not monocyte-derived macrophages, is dependent on recognition of microbial stimuli, as MHCII expression is significantly downregulated in germ-free, antibiotic-treated and MyD88 deficient mice. To address the function of MHCII presentation by intestinal macrophages we established two models of macrophage-specific MHCII deficiency. We observed a significant reduction in the overall frequency and number of tissue-resident, but not newly arrived, SI CD4 T cells in the absence of macrophage-expressed MHCII. Our data suggest that macrophage MHCII provides signals regulating gut CD4 T cell maintenance with different requirements in the SI and colon.
巨噬细胞通常被认为是抗原呈递细胞。然而，它们呈现抗原的能力以及调节巨噬细胞 MHCII 表达的因素还了解甚少。在这里，我们证明了肠道巨噬细胞 MHCII 的表达受到其在小肠（SI）或结肠中的位置、它们的个体发生以及肠道微生物群的差异调控。单核细胞衍生的巨噬细胞在组织来源、微生物状态或小鼠年龄的影响下均表达 MHCII，这表明存在共同的单核细胞分化途径。相比之下，出生后，寿命长、先天衍生的 Tim4 巨噬细胞上的 MHCII 表达水平较低，但在 SI 和结肠中的断奶时显著增加。此外，结肠中的 Tim4 上的 MHCII 表达，但不是单核细胞衍生的巨噬细胞上的 MHCII 表达，依赖于对微生物刺激的识别，因为在无菌、抗生素处理和 MyD88 缺陷小鼠中，MHCII 表达显著下调。为了研究肠道巨噬细胞 MHCII 呈递的功能，我们建立了两种巨噬细胞特异性 MHCII 缺陷模型。我们观察到，在缺乏巨噬细胞表达的 MHCII 时，组织驻留的，但不是新到达的 SI CD4 T 细胞的总体频率和数量明显减少。我们的数据表明，巨噬细胞 MHCII 提供了调节肠道 CD4 T 细胞维持的信号，在 SI 和结肠中具有不同的要求。
