感染和炎症刺激CD74+帕内斯细胞子集的扩张,以调节疾病进展
Iyshwarya Balasubramanian1, Sheila Bandyopadhyay1, Juan Flores1
1Department of Biological Sciences, Rutgers University, Newark, NJ, USA.
感染扩大了特定的帕内斯细胞 (PC) 子集,其特征是CD74表达,这推动了炎症性疾病的进展. 这种CD74+PC扩张是由MyD88和Mptx2调解的,突出了宿主-微生物相互作用的新机制.
科学领域:
- 免疫学 免疫学 免疫学
- 胃肠病学 胃肠病学
- 微生物学 微生物学
背景情况:
- 小肠中的帕内斯细胞 (PCs) 对于对抗微生物和环境挑战的宿主防御至关重要.
- 微生物影响PC组成和调节肠道炎症的确切机制尚未完全理解.
研究的目的:
- 研究共生和致病微生物如何改变帕内特细胞的组成和功能.
- 阐明特定的帕内斯细胞子集在炎症性疾病进展中的作用.
主要方法:
- 在常规和 gnotobiotic 条件下利用了新的 Paneth 细胞记者小鼠.
- 进行单细胞转录组分析以评估PC异质性对微生物刺激的反应.
- 通过基因废除模型研究了MyD88和Mptx2在PC反应和疾病发病的作用.
主要成果:
- 感染导致CD74阳性 (CD74+) 帕内斯细胞种群的扩大.
- CD74+ PCs的数量与小鼠的炎症性疾病的严重程度有积极的相关性,这一发现反映在人类炎症组织中.
- 感染诱导的细胞因子刺激活性PC中的反应性氧物种 (ROS) 生产和Mptx2表达.
- 在PC中切除MyD88或Mptx2可改善病原体诱导的全身炎症.
结论:
- 感染触发了特定的帕内斯细胞子集 (CD74+) 的扩张,该子集在调节炎症疾病进展方面发挥着重要作用.
- MyD88-Mptx2通路对于感染诱导的帕内斯细胞激活和扩张至关重要,提供潜在的治疗点.
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