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Published on: May 31, 2018

The macrophage PELI1-JAK2/STAT3-secretome axis: a potential target for ameliorating septic inflammation and

Yi Huang1, Lizhen Xuan1, Kunlin Zhou1

  • 1Department of Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China

Acta Biochimica Et Biophysica Sinica
|July 7, 2026
PubMed

Insights

PELI1 in macrophages exacerbates sepsis by promoting inflammation and coagulation dysfunction via the JAK2/STAT3 pathway. Targeting the PELI1-secretome axis may offer a novel therapeutic strategy for sepsis.

Area of Science:

  • Immunology
  • Molecular Biology
  • Pathophysiology

Background:

  • Sepsis is a life-threatening condition characterized by dysregulated inflammation and coagulation.
  • Macrophage dysfunction plays a critical role in sepsis progression.
  • The specific role of PELI1 in sepsis-induced pathology remains unclear.

Purpose of the Study:

  • To investigate the role of PELI1 in macrophage-mediated inflammation and coagulation dysfunction during sepsis.
  • To elucidate the underlying molecular mechanisms involving the JAK2/STAT3 signaling pathway.
  • To identify the PELI1-secretome axis as a potential therapeutic target.

Main Methods:

  • Analysis of single-cell RNA-seq data from septic patients.
  • Establishment of a murine sepsis model (cecal ligation and puncture).
  • Gene knockdown of PELI1 in macrophages (in vitro and in vivo).
  • Assessment of inflammatory markers, coagulation factors, and tissue injury.
  • Western blotting, RT-qPCR, ELISA, H&E staining, and immunohistochemistry.

Main Results:

  • PELI1 is significantly upregulated in monocytes of non-surviving septic patients and in septic mice.
  • PELI1 upregulation correlates with severe inflammation and coagulation dysfunction.
  • PELI1 knockout suppresses JAK2/STAT3 activation, reducing pro-inflammatory and pro-coagulant factor secretion.
  • Transfer of secretome from PELI1-knockout macrophages ameliorates sepsis pathology in wild-type mice.

Conclusions:

  • PELI1 mediates sepsis-induced tissue injury by regulating macrophage secretome via the JAK2/STAT3 pathway.
  • The PELI1-secretome axis is a key driver of sepsis pathology.
  • Targeting PELI1 presents a promising therapeutic avenue for sepsis treatment.
Keywords:
JAK2/STAT3 signaling pathwayPELI1coagulation dysfunctionmacrophagesepsis

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