The increased marginal zone B cells attenuates early inflammatory responses during sepsis in Gpr174 deficient mice.

Abstract

GPR174 plays a crucial role in immune responses, but the role of GPR174 in the pathological progress of sepsis remains incompletely understood. In this study, we generated a sepsis model by cecal ligation and puncture (CLP) to investigate the role of GPR174 in regulating functions and underlying mechanism of marginal zone B (MZ B) cells in sepsis. We found that in Gpr174 deficient mice, the number of splenic MZ B cells was increased. Moreover, Gpr174-/- MZ B cells exhibited an enhanced response to LPS stimulation in vitro. By using the CLP-induced sepsis model, we demonstrated that the increased MZ B cells attenuated early inflammatory responses during sepsis. RNA sequencing results revealed that the expression of c-fos in splenic B lymphocytes was upregulated in Gpr174 deficient mice. However, the protective role of increased MZ B cells in Gpr174 deficient mice was weakened by a c-fos-specific inhibitor. Collectively, these findings suggested that GPR174 plays an immunomodulatory role in early immune responses during sepsis through the regulation of MZ B cells.

• Authors: Ming Zhu, Chong Li, Zhenju Song, Sucheng Mu, Jianli Wang, Wei Wei, Yi Han, Dongze Qiu, Xun Chu, Chaoyang Tong
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 81 Pg. 106034 (Apr 2020) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 31786099 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• 3-(5-(4-(cyclopentyloxy)-2-hydroxybenzoyl)-2-((3-hydroxy-1,2-benzisoxazol-6-yl)methoxy)phenyl)propionic acid
• Benzophenones
• GPR174 protein, mouse
• Isoxazoles
• Lipopolysaccharides
• Proto-Oncogene Proteins c-fos
• Receptors, G-Protein-Coupled

Topics

• Animals
• B-Lymphocytes (drug effects, immunology, metabolism)
• Benzophenones (administration & dosage)
• Disease Models, Animal
• Humans
• Isoxazoles (administration & dosage)
• Lipopolysaccharides (immunology)
• Mice
• Mice, Knockout
• Proto-Oncogene Proteins c-fos (antagonists & inhibitors, metabolism)
• RNA-Seq
• Receptors, G-Protein-Coupled (deficiency, genetics)
• Sepsis (immunology, pathology)
• Signal Transduction (drug effects, genetics, immunology)
• Spleen (cytology, immunology)
• Up-Regulation (drug effects, immunology)