The increased marginal zone B cells attenuates early inflammatory responses during sepsis in Gpr174 deficient mice |
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Affiliation: | 1. Scuola Superiore Sant''Anna, Pisa, Pisa, Italy;2. Institute of Clinical Physiology of CNR, Pisa, Italy;3. Harvard Department of Stem Cell and Regenerative Biology, Cambridge, MA, USA;1. Laboratori de Medicina Computacional, Unitat de Bioestadística, Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain;2. Department of Biochemistry and Physiology, School of Pharmacy, Universitat de Barcelona, Barcelona, Spain;3. Centro de Investigación en Red, Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain;4. Molecular Neurobiology laboratory, Department of Biochemistry and Molecular Biomedicine, Universitat de Barcelona, Barcelona, Spain |
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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. |
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Keywords: | Sepsis MZ B cells MZ B" },{" #name" :" keyword" ," $" :{" id" :" k0030" }," $$" :[{" #name" :" text" ," _" :" marginal zone B FO B" },{" #name" :" keyword" ," $" :{" id" :" k0040" }," $$" :[{" #name" :" text" ," _" :" follicular B T1 B" },{" #name" :" keyword" ," $" :{" id" :" k0050" }," $$" :[{" #name" :" text" ," _" :" type 1 transitional B T2 B" },{" #name" :" keyword" ," $" :{" id" :" k0060" }," $$" :[{" #name" :" text" ," _" :" type 2 transitional B DE" },{" #name" :" keyword" ," $" :{" id" :" k0070" }," $$" :[{" #name" :" text" ," _" :" differentially expressed FC" },{" #name" :" keyword" ," $" :{" id" :" k0080" }," $$" :[{" #name" :" text" ," _" :" fold change |
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