Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 119, Issue 48, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2211230119
Keywords
hematopoietic stem cell transplantation; microbiota; granulopoiesis; neutropenia; Ruminococcaceae
Categories
Funding
- Japan Society for the Promotion of Science KAKENHI [25293217, 20K21610, 21K08409, 21K16259, 20K17366]
- Center of Innovation Program of JST
- COI-NEXT of JST [JPMJPF2108]
- Suhara Memorial Foundation
- Promotion and Standardization of the Tenure-Track System
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This study reveals an interaction between gut microbiota and neutropenia after syngeneic hematopoietic stem cell transplantation and chemotherapy, suggesting their potential in stimulating reactive granulopoiesis.
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.
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