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Klf4 protects thymus integrity during late pregnancy.
Depoërs, Lucyle; Dumont-Lagacé, Maude; Trinh, Vincent Quoc-Huy; Houques, Chloé; Côté, Caroline; Larouche, Jean-David; Brochu, Sylvie; Perreault, Claude.
Afiliación
  • Depoërs L; Department of Medicine, Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, Canada.
  • Dumont-Lagacé M; ExCellThera, Inc., Montréal, QC, Canada.
  • Trinh VQ; Piercing Star Technologies, Rabat, Morocco.
  • Houques C; Department of Medicine, Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, Canada.
  • Côté C; Department of Pathology and Cellular Biology, Institute for Research in Immunology and Cancer, and Centre de recherche du Centre hospitalier de l'Université de Montréal, Université de Montréal, Montréal, QC, Canada.
  • Larouche JD; Institut de Génétique Moléculaire de Montpellier, Université de Montpellier, Montpellier, France.
  • Brochu S; Department of Medicine, Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, Canada.
  • Perreault C; Department of Medicine, Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, Canada.
Front Immunol ; 14: 1016378, 2023.
Article en En | MEDLINE | ID: mdl-37180153
Pregnancy causes abrupt thymic atrophy. This atrophy is characterized by a severe decrease in the number of all thymocyte subsets and qualitative (but not quantitative) changes in thymic epithelial cells (TECs). Pregnancy-related thymic involution is triggered by progesterone-induced functional changes affecting mainly cortical TECs (cTECs). Remarkably, this severe involution is rapidly corrected following parturition. We postulated that understanding the mechanisms of pregnancy-related thymic changes could provide novel insights into signaling pathways regulating TEC function. When we analyzed genes whose expression in TECs was modified during late pregnancy, we found a strong enrichment in genes bearing KLF4 transcription factor binding motifs. We, therefore, engineered a Psmb11-iCre : Klf4lox/lox mouse model to study the impact of TEC-specific Klf4 deletion in steady-state conditions and during late pregnancy. Under steady-state conditions, Klf4 deletion had a minimal effect on TEC subsets and did not affect thymic architecture. However, pregnancy-induced thymic involution was much more pronounced in pregnant females lacking Klf4 expression in TECs. These mice displayed a substantial ablation of TECs with a more pronounced loss of thymocytes. Transcriptomic and phenotypic analyses of Klf4 -/- TECs revealed that Klf4 maintains cTEC numbers by supporting cell survival and preventing epithelial-to-mesenchymal plasticity during late pregnancy. We conclude that Klf4 is essential for preserving TEC's integrity and mitigating thymic involution during late pregnancy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Timo / Timocitos Tipo de estudio: Prognostic_studies / Qualitative_research Límite: Animals / Pregnancy Idioma: En Revista: Front Immunol Año: 2023 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Timo / Timocitos Tipo de estudio: Prognostic_studies / Qualitative_research Límite: Animals / Pregnancy Idioma: En Revista: Front Immunol Año: 2023 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Suiza