Celiac disease (CD) is an immune-driven disease characterized by tissue damage in the small intestine of genetically-susceptible individuals. We evaluated here a crucial immune regulatory pathway involving TYRO3, AXL, and MERTK (TAM) receptors and their ligands PROS1 and GAS6 in duodenal biopsies of controls and CD patients. We found increased GAS6 expression associated with downregulation of PROS1 and variable TAM receptors levels in duodenum tissue of CD patients. Interestingly, CD3 lymphocytes, CD68, CD11c myeloid and epithelial cells, showed differential expressions of TAM components comparing CD vs controls. Principal component analysis revealed a clear segregation of two groups of CD patients based on TAM components and IFN signaling. In vitro validation demonstrated that monocytes, T lymphocytes and epithelial cells upregulated TAM components in response to IFN stimulation. Our findings highlight a dysregulated TAM axis in CD related to IFN signaling and contribute to a deeper understanding of the pathophysiology of CD.

中文翻译：

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未经治疗的乳糜泻患者的十二指肠粘膜 GAS6 和 PROS1 以及负调节酪氨酸激酶 TAM 受体亚家族的表达发生改变

乳糜泻（CD）是一种免疫驱动的疾病，其特征是遗传易感个体的小肠组织损伤。我们在对照和 CD 患者的十二指肠活检中评估了涉及 TYRO3、AXL 和 MERTK (TAM) 受体及其配体 PROS1 和 GAS6 的关键免疫调节途径。我们发现 CD 患者十二指肠组织中 GAS6 表达增加与 PROS1 和可变 TAM 受体水平下调相关。有趣的是，与对照组相比，CD3 淋巴细胞、CD68、CD11c 骨髓细胞和上皮细胞显示出 TAM 成分的差异表达。主成分分析显示，根据 TAM 成分和 IFN 信号传导，两组 CD 患者存在明显的分离。体外验证表明，单核细胞、T 淋巴细胞和上皮细胞响应 IFN 刺激而上调 TAM 成分。我们的研究结果强调了 CD 中与 IFN 信号传导相关的 TAM 轴失调，有助于更深入地了解 CD 的病理生理学。