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

JCI Insight. 2021 Aug 23;6(16):e148652. doi: 10.1172/jci.insight.148652.


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.

Keywords: Bone marrow differentiation; Cell Biology; Immunology; Neutrophils.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow / growth & development*
  • CD40 Antigens / metabolism*
  • CD40 Ligand / genetics
  • CD40 Ligand / metabolism*
  • Cell Differentiation / genetics
  • Cell Movement / genetics
  • Cells, Cultured
  • Female
  • Gene Expression Regulation, Developmental
  • Hematopoiesis / genetics*
  • Mice
  • Mice, Knockout
  • Models, Animal
  • Neutrophils / physiology*
  • RNA-Seq
  • Signal Transduction / genetics


  • CD40 Antigens
  • CD40 Ligand