TY - JOUR
T1 - CD40L modulates transcriptional signatures of neutrophils in the bone marrow associated with development and trafficking
AU - França, Tábata Takahashi
AU - Al-Sbiei, Ashraf
AU - Bashir, Ghada
AU - Mohamed, Yassir Awad
AU - Salgado, Ranieri Coelho
AU - Barreiros, Lucila Akune
AU - da Silva Napoleão, Sarah Maria
AU - Weber, Cristina Worm
AU - Ferreira, Janaíra Fernandes Severo
AU - Aranda, Carolina Sanchez
AU - Prando, Carolina
AU - de Barros Dorna, Mayra B.
AU - Jurisica, Igor
AU - Fernandez-Cabezudo, Maria J.
AU - Ochs, Hans D.
AU - Condino-Neto, Antonio
AU - Al-Ramadi, Basel K.
AU - Cabral-Marques, Otavio
N1 - Funding Information:
This work was supported by grants from Fundação de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) process number 2017/04187-9 to TTF; processes numbers 2018/18886-9, 2020/01688-0, and 2020/07069-0 to OCM; and process number 2016/22158-3 to ACN. This work was supported by The Jeffrey Modell Foundation to ACN and HDO; by Hyper IgM Foundation to TTF and ACN; and by Research Grants Committee of the College of Medicine & Health Sciences, UAE University, grant NP-19-15, to BKAR. Computational analyses (IJ) were in part supported by the grants from Ontario Research Fund (grant 34876); Natural Sciences Research Council (NSERC; 203475); Canada Foundation for Innovation (CFI; 29272, 225404, 33536); and Buchan Foundation, Ian Lawson van Toch Fund, and IBM (the funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript) to IJ. We thank Thiago Domingues Crespo Hirata for his explanations on how to use CemiTool. We also thank Paula Freire for her kind instructions about Morpheus and NetworkAnalyst usage. We acknowledge Nadia El Khawanky from the Department of Hematology and Oncology, Faculty of Medicine, The University of Freiburg, for critical reading of the manuscript. Finally, we thank our patients and their families for kindly accepting to participate in this study.
Publisher Copyright:
© 2021, França et al.
PY - 2021/8/23
Y1 - 2021/8/23
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85113410913&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85113410913&partnerID=8YFLogxK
U2 - 10.1172/jci.insight.148652
DO - 10.1172/jci.insight.148652
M3 - Article
C2 - 34255742
AN - SCOPUS:85113410913
SN - 2379-3708
VL - 6
JO - JCI insight
JF - JCI insight
IS - 16
M1 - e148652
ER -