IL-1/IL-1R在急性炎症中对髓系造血的调控作用及机制研究

对于血液肿瘤患者，在接受化疗或造血干细胞移植后造血重建的过程中，由于粒细胞缺乏，感染严重细菌、真菌等病原体的风险明显增加。缩短粒细胞缺乏持续时间，有效促进粒系造血恢复，可提高化疗后或移植后患者生存率。IL-1/IL-1R通路的活化被报道在一定程度上可调控髓系造血，但相关机制尚不明确。在前期的研究中我们发现，造血干祖细胞可表现出“强化髓系造血”，即机体受到连续炎症刺激后，相较于经典急性髓系造血，可更加迅速启动髓系造血，粒系前体细胞大量增殖，骨髓成熟中性粒细胞迅速动员至外周。更重要的是，“强化髓系造血”可缩短照射后粒细胞缺乏的持续时间，并且该过程需要依赖于IL-1/IL-1R通路的活化。基于以上研究背景，我们拟进一步研究“强化髓系造血”的表型特点，明确IL-1/IL-1R通路的活化对促进髓系造血调控作用的分子机制，揭示若干与髓系造血相关的分子靶点，为临床移植或化疗后造血恢复提供新的靶标。

Most patients with hematological malignancies take great risks of severe infection after chemotherapy or hematopoietic stem cell transplantation, due to prolonged neutropenia. Promoting granulopoiesis recovery, shorten neutropenia duration could significantly increase outcomes after chemotherapy or transplantation. However, there is still controversy about how to promote granulopoiesis. We found that recurring infection induced enhanced myelopoiesis, which elicited instant neutrophils mobilization from the BM, instantly elevating peripheral blood, and augmented granulocyte/monocyte progenitors proliferation. Enhanced granulopoiesis is critical for host defense against recurrent infections. Here, using single-cell RNA sequencing, we show that IL-1/IL-1R signaling is specifically activated and required for enhanced myelopoiesis. This mechanism provides a new strategy for accelerating BM recovery and augmenting host defenses in neutropenia infectious diseases.