Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Immune Environment in Glioblastoma (Feb 2023)
    • Korsmeyer Award 25th Anniversary Collection (Jan 2023)
    • Aging (Jul 2022)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • Circadian Rhythm (Oct 2021)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Research letters
    • Letters to the editor
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Research letters
  • Letters to the editor
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
SLAMF7 regulates the inflammatory response in macrophages during polymicrobial sepsis
Yongjian Wu, … , Lei Liu, Xi Huang
Yongjian Wu, … , Lei Liu, Xi Huang
Published February 7, 2023
Citation Information: J Clin Invest. 2023;133(6):e150224. https://doi.org/10.1172/JCI150224.
View: Text | PDF
Research Article Infectious disease Inflammation

SLAMF7 regulates the inflammatory response in macrophages during polymicrobial sepsis

  • Text
  • PDF
Abstract

Uncontrolled inflammation occurred in sepsis results in multiple organ injuries and shock, which contributes to the death of patients with sepsis. However, the regulatory mechanisms that restrict excessive inflammation are still elusive. Here, we identified an Ig-like receptor called signaling lymphocyte activation molecular family 7 (SLAMF7) as a key suppressor of inflammation during sepsis. We found that the expression of SLAMF7 on monocytes/macrophages was significantly elevated in patients with sepsis and in septic mice. SLAMF7 attenuated TLR-dependent MAPK and NF-κB signaling activation in macrophages by cooperating with Src homology 2–containing inositol-5′‑phosphatase 1 (SHIP1). Furthermore, SLAMF7 interacted with SHIP1 and TNF receptor–associated factor 6 (TRAF6) to inhibit K63 ubiquitination of TRAF6. In addition, we found that tyrosine phosphorylation sites within the intracellular domain of SLAMF7 and the phosphatase domain of SHIP1 were indispensable for the interaction between SLAMF7, SHIP1, and TRAF6 and SLAMF7-mediated modulation of cytokine production. Finally, we demonstrated that SLAMF7 protected against lethal sepsis and endotoxemia by downregulating macrophage proinflammatory cytokines and suppressing inflammation-induced organ damage. Taken together, our findings reveal a negative regulatory role of SLAMF7 in polymicrobial sepsis, thus providing sights into the treatment of sepsis.

Authors

Yongjian Wu, Qiaohua Wang, Miao Li, Juanfeng Lao, Huishu Tang, Siqi Ming, Minhao Wu, Sitang Gong, Linhai Li, Lei Liu, Xi Huang

×

Graphical abstract

Options: View larger image (or click on image)

Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts