糖皮质激素是类固醇激素，以其有效的抗炎作用而闻名。然而，它们的免疫调节特性是多方面的。越来越多的证据表明，糖皮质激素信号传导可促进有效的免疫，而糖皮质激素信号传导的破坏会损害免疫功能。在这项研究中，我们使用 LysM-Cre 驱动程序 (myGRKO) 有条件地删除了骨髓谱系中的糖皮质激素受体 (GR)。我们研究了幽门螺杆菌对巨噬细胞激活和胃免疫反应的影响，幽门螺杆菌是胃癌最著名的危险因素。我们的结果表明，与 WT 相比，GRKO 巨噬细胞在无类固醇条件下表现出更高的促炎基因表达。然而，当在体内受到挑战时，GRKO 巨噬细胞表现出异常的染色质景观和受损的促炎基因表达谱。此外，幽门螺杆菌的胃定植表明 myGRKO 小鼠胃免疫反应受损，T 细胞募集减少。结果，myGRKO 小鼠免受萎缩性胃炎和幽门化生的影响。这些结果表明糖皮质激素信号在准备巨噬细胞响应细菌感染和限制其致病性激活方面具有双重作用。此外，我们的结果支持巨噬细胞对于胃幽门螺杆菌免疫至关重要。

Glucocorticoids are steroid hormones well-known for their potent anti-inflammatory effects. However, their immunomodulatory properties are multifaceted. Increasing evidence suggests that glucocorticoid signaling promotes effective immunity and that disruption of glucocorticoid signaling impairs immune function. In this study, we conditionally deleted the glucocorticoid receptor (GR) in the myeloid lineage using the LysM-Cre driver (myGRKO). We examined the impact on macrophage activation and gastric immune responses to Helicobacter pylori, the best-known risk factor of gastric cancer. Our results indicate that, compared to WT, GRKO macrophages exhibited higher expression of proinflammatory genes in steroid-free conditions. However, when challenged in vivo, GRKO macrophages exhibited aberrant chromatin landscapes and impaired proinflammatory gene expression profiles. Moreover, gastric colonization with Helicobacter pylori revealed impaired gastric immune responses and reduced T cell recruitment in myGRKO mice. As a result, myGRKO mice were protected from atrophic gastritis and pyloric metaplasia development. These results demonstrate a dual role for glucocorticoid signaling in preparing macrophages to respond to bacterial infection but limiting their pathogenic activation. In addition, our results support that macrophages are critical for gastric Helicobacter pylori immunity.