CD40L modulates transcriptional signatures of neutrophils in the bone marrow associated with development and trafficking

Neutrophils are produced in the BM in a process called granulopoiesis, in which progenitor cells sequentially develop into mature neutrophils. During the developmental process, which is finely regulated by distinct transcription factors, neutrophils acquire the ability to exit the BM, properly distr...

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Bibliographic Details
Published in:	JCI insight Vol. 6; no. 16
Main Authors:	França, Tábata Takahashi, Al-Sbiei, Ashraf, Bashir, Ghada, Mohamed, Yassir Awad, Salgado, Ranieri Coelho, Barreiros, Lucila Akune, Maria da Silva Napoleão, Sarah, Weber, Cristina Worm, Fernandes Severo Ferreira, Janaíra, Aranda, Carolina Sanchez, Prando, Carolina, de Barros Dorna, Mayra B, Jurisica, Igor, Fernandez-Cabezudo, Maria J, Ochs, Hans D, Condino-Neto, Antonio, Al-Ramadi, Basel K, Cabral-Marques, Otavio
Format:	Journal Article
Language:	English
Published:	United States American Society for Clinical Investigation 23-08-2021 American Society for Clinical investigation
Subjects:	Animals Bone Marrow - growth & development CD40 Antigens - metabolism CD40 Ligand - genetics CD40 Ligand - metabolism Cell biology Cell Differentiation - genetics Cell Movement - genetics Cells, Cultured Female Gene Expression Regulation, Developmental Hematopoiesis - genetics Immunology Mice Mice, Knockout Models, Animal Neutrophils - physiology Resource and Technical Advance RNA-Seq Signal Transduction - genetics Immunology Bone marrow differentiation Neutrophils Cell Biology
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Summary:	Neutrophils are produced in the BM in a process called granulopoiesis, in which progenitor cells sequentially develop into mature neutrophils. During the developmental process, which is finely regulated by distinct transcription factors, neutrophils acquire the ability to exit the BM, properly distribute throughout the body, and migrate to infection sites. Previous studies have demonstrated that CD40 ligand (CD40L) influences hematopoiesis and granulopoiesis. Here, we investigate the effect of CD40L on neutrophil development and trafficking by performing functional and transcriptome analyses. We found that CD40L signaling plays an essential role in the early stages of neutrophil generation and development in the BM. Moreover, CD40L modulates transcriptional signatures, indicating that this molecule enables neutrophils to traffic throughout the body and to migrate in response to inflammatory signals. Thus, our study provides insights into the complex relationships between CD40L signaling and granulopoiesis, and it suggests a potentially novel and nonredundant role of CD40L signaling in neutrophil development and function.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Authorship note: ACN, BKAR, and OCM contributed equally to this work.
ISSN:	2379-3708 2379-3708
DOI:	10.1172/jci.insight.148652