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

Author(s):Show less -

Franca, Tabata Takahashi ^[1] ; Al-Sbiei, Ashraf ^[2] ; Bashir, Ghada ^[2] ; Mohamed, Yassir Awad ^[2] ; Salgado, Ranieri Coelho ^[1] ; Barreiros, Lucila Akune ^[1] ; da Silva Napoleao, Sarah Maria ^[1] ; Weber, Cristina Worm ^[3] ; Severo Ferreira, Janaira Fernandes ^[4] ; Aranda, Carolina Sanchez ^[5] ; Prando, Carolina ^{[6, 7]} ; de Barros Dorna, Mayra B. ^[8] ; Jurisica, Igor ^{[9, 10, 11]} ; Fernandez-Cabezudo, Maria J. ^[12] ; Ochs, Hans D. ^[13] ; Condino-Neto, Antonio ^[1] ; Al-Ramadi, Basel K. ^{[2, 14]} ; Cabral-Marques, Otavio ^{[15, 1, 16]}

Affiliation:Show less -

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, 1730 Lineu Prestes Ave, BR-05508000 Sao Paulo, SP - Brazil

^[2] United Arab Emirates UAE Univ, Coll Med & Hlth Sci, Dept Med Microbiol & Immunol, Abu Dhabi - U Arab Emirates

^[3] Pediat Allergy & Immunol Clin, Caxias Do Sul, RS - Brazil

^[4] Albert Sabin Hosp, Fortaleza, Ceara - Brazil

^[5] Univ Fed Sao Paulo, Dept Pediat, Div Allergy Immunol & Rheumatol, Sao Paulo, SP - Brazil

^[6] Hosp Pequeno Principe, Curitiba, Parana - Brazil

^[7] Pele Pequeno Principe Res Intitute, Fac Pequeno Principe, Curitiba, Parana - Brazil

^[8] Hosp Clin Sao Paulo, Childrens Inst, Dept Pediat, Div Allergy & Immunol, Sao Paulo, SP - Brazil

^[9] Univ Toronto, Dept Med Biophys, Univ Hlth Network, Krembil Res Inst, Div Orthoped Surg, Schroeder Arth, Schroeder Arthrit Inst, Osteoarthrit Res Program, Toronto, ON - Canada

^[10] Univ Toronto, Dept Comp Sci, Univ Hlth Network, Krembil Res Inst, Div Orthoped Surg, Schroeder Arth, Schroeder Arthrit Inst, Osteoarthrit Res Program, Toronto, ON - Canada

^[11] Slovak Acad Sci, Inst Neuroimmunol, Bratislava - Slovakia

^[12] UAE Univ, Coll Med & Hlth Sci, Dept Biochem & Mol Biol, Abu Dhabi - U Arab Emirates

^[13] Univ Washington, Sch Med, Dept Pediat, Seattle Childrens Res Inst, Seattle, WA 98195 - USA

^[14] UAE Univ, Zayed Ctr Hlth Sci, Abu Dhabi - U Arab Emirates

^[15] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Sao Paulo, SP - Brazil

^[16] Universal Sci Educ & Res Network USERN, Network Immun Infect Malignancy & Autoimmun NIIMA, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: JCI INSIGHT; v. 6, n. 16 AUG 23 2021.
• Web of Science Citations: 0

Abstract

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. (AU)

• FAPESP's process: 16/22158-3 - Molecular genetic mechanisms of primary immunodeficiencies
• Grantee: Antonio Condino Neto
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 20/01688-0 - Systemic and integrative analysis of the immune response to Zika and Dengue viral infections
• Grantee: Otávio Cabral Marques
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 18/18886-9 - Systemic and integrative analysis of the immune response to Zika and Dengue viral infections
• Grantee: Otávio Cabral Marques
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 17/04187-9 - Functional evaluation of neutrophils in CD40L-DEFICIENCY patients
• Grantee: Tábata Takahashi França
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 20/07069-0 - Systemic and integrative analysis of T lymphocyte exhaustion mechanisms in patients with COVID-19
• Grantee: Otávio Cabral Marques
• Support Opportunities: Regular Research Grants