2. Academic Validation
  3. FXR protects against neonatal sepsis by enhancing the immunosuppressive function of MDSCs

FXR protects against neonatal sepsis by enhancing the immunosuppressive function of MDSCs

  • Cell Mol Immunol. 2025 Jun;22(6):661-673. doi: 10.1038/s41423-025-01289-4.
Juan He # 1 2 3,  Yuxin Zhang # 2,  Yuchao Jing # 2 4,  Rui Dong 2,  Tongyang Li 2,  Xiaoqing Zheng 1,  Pan Zhou 2,  Kun Shi 5,  Wei Zhong 3,  Qiang Liu 6,  Jie Zhou 7 8
Affiliations

Affiliations

  • 1 Laboratory of Immunity, Inflammation & Cancer, Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
  • 2 Tianjin Institute of Immunology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), State Key Laboratory of Experimental Hematology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China.
  • 3 Guangdong Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China.
  • 4 Department of Immunology, Basic Medical College, Changzhi Medical College, Changzhi, 046000, China.
  • 5 Department of Obstetrics and Gynecology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China.
  • 6 Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300050, China.
  • 7 Laboratory of Immunity, Inflammation & Cancer, Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. zhoujie@tmu.edu.cn.
  • 8 Tianjin Institute of Immunology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), State Key Laboratory of Experimental Hematology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China. zhoujie@tmu.edu.cn.
  • # Contributed equally.
PMID: 40335739 DOI: 10.1038/s41423-025-01289-4
Abstract

Myeloid-derived suppressor cells (MDSCs) play a protective role against neonatal inflammation during the early postnatal period. However, the mechanisms regulating neonatal MDSC function remain to be fully elucidated. In this study, we report that the bile acid receptor farnesoid X receptor (FXR) acts as a positive regulator of neonatal MDSC function. The FDA-approved FXR Agonist obeticholic acid (OCA) protects against neonatal sepsis in an FXR-dependent manner. Genetic deficiency of FXR impairs the immunosuppressive and Antibacterial functions of MDSCs, thereby exacerbating the severity of neonatal sepsis. Adoptive transfer of MDSCs alleviates sepsis in both FXR-/- and FXRfl/flMrp8-Cre+ pups. Mechanistic studies revealed that Hif1α, a well-established regulator of MDSCs, is a direct transcriptional target of FXR. In patients with neonatal sepsis, downregulation of FXR and HIF-1α in MDSCs was observed, which was inversely correlated with clinical parameters. These observations demonstrate the importance of FXR in neonatal MDSC function and its therapeutic potential in neonatal sepsis.

Keywords

Farnesoid X receptor; Myeloid-derived suppressor cells; Neonatal sepsis.

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