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Reactive granulopoiesis depends on T-cell production of IL-17A and neutropenia-associated alteration of gut microbiota
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.4 ) Pub Date : 2022-11-21 , DOI: 10.1073/pnas.2211230119
Xuanzhong Chen 1 , Daigo Hashimoto 1 , Ko Ebata 1 , Shuichiro Takahashi 1 , Yu Shimizu 2 , Ryuga Shinozaki 3 , Yuta Hasegawa 1 , Ryo Kikuchi 1 , Hajime Senjo 1 , Kazuki Yoneda 1 , Zixuan Zhang 1 , Shinpei Harada 1 , Eiko Hayase 1 , Takahide Ara 1 , Hiroyuki Ohigashi 1 , Yoichiro Iwakura 4 , Kiminori Nakamura 2 , Tokiyoshi Ayabe 2 , Takanori Teshima 1
Affiliation  

Granulopoiesis in the bone marrow adjusts cellular output as demand for neutrophils changes. Reactive granulopoiesis is induced by profound neutropenia, but its mechanism remains to be clarified. We herein explored its mechanisms using mouse models of syngeneic hematopoietic stem cell transplantation (SCT) and 5-fluorouracil-induced neutropenia. After SCT, T cell production of IL-17A was up-regulated. Neutrophil recovery was significantly delayed in IL-17A-deficient or T cell-deficient RAG1 −/− mice, and adoptive transfer of wild-type ( WT ) T cells facilitated neutrophil engraftment. Gut decontamination with oral antibiotics suppressed T cell production of IL-17A and impaired neutrophil recovery. Transplantation of fecal microbiota collected from neutropenic, not naive, mice promoted neutrophil recovery in these mice, suggesting that neutropenia-associated microbiota had a potential to stimulate reactive granulopoiesis. Our study uncovered a cross talk between gut microbiota and neutropenia after SCT and chemotherapy.

中文翻译:

反应性粒细胞生成取决于 IL-17A 的 T 细胞产生和中性粒细胞减少相关的肠道菌群改变

随着对中性粒细胞需求的变化,骨髓中的粒细胞生成调节细胞输出。反应性粒细胞生成是由严重的中性粒细胞减少引起的,但其机制仍有待阐明。我们在此使用同基因造血干细胞移植 (SCT) 和 5-氟尿嘧啶诱导的中性粒细胞减少症的小鼠模型探讨了其机制。SCT 后,T 细胞产生的 IL-17A 被上调。IL-17A 缺陷或 T 细胞缺陷的中性粒细胞恢复显着延迟RAG1-/- 小鼠,以及野生型的过继转移(重量) T 细胞促进中性粒细胞植入。用口服抗生素净化肠道会抑制 T 细胞产生 IL-17A,并损害中性粒细胞的恢复。从中性粒细胞减少症而非幼稚小鼠收集的粪便微生物群的移植促进了这些小鼠中性粒细胞的恢复,表明与中性粒细胞减少症相关的微生物群有可能刺激反应性粒细胞生成。我们的研究揭示了 SCT 和化疗后肠道微生物群与中性粒细胞减少症之间的相互作用。
更新日期:2022-11-21
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