Semaphorin 3A contributes to sepsis‑induced immunosuppression by impairing CD4+ T cell anergy.

Abstract

Semaphorin 3A (Sema3A), a member of the Sema family of proteins, appears to serve an important role in sepsis and sepsis‑induced immunosuppression and has been regarded as a crucial regulator involved in cellular immune response. However, the role of Sema3A in CD4+ T cell anergy during sepsis remains to be elucidated. In the present study, the cecal ligation and perforation model and lipopolysaccharide (LPS) were used to simulate sepsis and the role of Sema3A in sepsis‑induced CD4+ T cell anergy was investigated in vivo and in vitro. In vivo, the serum concentration of Sema3A was enhanced and exacerbated sepsis‑induced T cell immunosuppression and multiple organ dysfunction syndromes (MODS). Administration of (‑)‑epigallocatechin‑3‑gallate, an inhibitor of Sema3A, markedly improved sepsis‑induced T cell immunosuppression and MODS. In vitro, both lymphoid and myeloid lineages secreted high concentration of Sema3A in LPS‑induced sepsis, especially in the lymphoid lineage. Inhibition of Sema3A alleviated T cell anergy. The NF‑κB signaling pathway was involved in Sema3A‑mediated autocrine loop aggravating T cell immune dysfunction during LPS‑induced sepsis. Inhibiting Sema3A exerted significant improvement of sepsis‑induced immunosuppression and MODS, which was associated with improvement of CD4+ T cells anergy via regulation of the NF‑κB signaling pathway.

• Authors: Yulei Gao, Chunxue Wang, Ziyi Wang, Wenjie Li, Yancun Liu, Songtao Shou, Yanfen Chai
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 23 Issue 4 (04 2021) ISSN: 1791-3004 [Electronic] Greece
• PMID: 33649856 (Publication Type: Journal Article)

Chemical References

• Antioxidants
• Lipopolysaccharides
• NF-kappa B
• Semaphorin-3A
• Catechin
• epigallocatechin gallate

Topics

• Animals
• Antioxidants (administration & dosage)
• CD4-Positive T-Lymphocytes (immunology, metabolism)
• Catechin (administration & dosage, analogs & derivatives)
• Cells, Cultured
• Clonal Anergy (immunology)
• Humans
• Immune Tolerance (immunology)
• Lipopolysaccharides (immunology)
• Male
• Mice, Inbred C57BL
• Multiple Organ Failure (immunology, metabolism, prevention & control)
• NF-kappa B (immunology, metabolism)
• Semaphorin-3A (antagonists & inhibitors, immunology, metabolism)
• Sepsis (immunology, metabolism)
• Signal Transduction (drug effects, immunology)
• Mice