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

Autor(es):Mostrar menos -

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]}

Afiliação do(s) autor(es):Mostrar menos -

^[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

• Tipo de documento: Artigo Científico
• Fonte: JCI INSIGHT; v. 6, n. 16 AUG 23 2021.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 16/22158-3 - Mecanismos genético-moleculares nas imunodeficiências primárias
• Beneficiário: Antonio Condino Neto
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 20/01688-0 - Análise sistêmica e integrativa da resposta imune às infecções virais por Zika e Dengue
• Beneficiário: Otávio Cabral Marques
• Modalidade de apoio: Bolsas no Brasil - Jovens Pesquisadores
• Processo FAPESP: 18/18886-9 - Análise sistêmica e integrativa da resposta imune às infecções virais por Zika e Dengue
• Beneficiário: Otávio Cabral Marques
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 17/04187-9 - Avaliação funcional de neutrófilos em pacientes com deficiência de cd40l
• Beneficiário: Tábata Takahashi França
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 20/07069-0 - Análise sistêmica e integrativa dos mecanismos de exaustão dos linfócitos T de pacientes com COVID-19
• Beneficiário: Otávio Cabral Marques
• Modalidade de apoio: Auxílio à Pesquisa - Regular