Open Access

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

  • Authors:
    • Yulei Gao
    • Chunxue Wang
    • Ziyi Wang
    • Wenjie Li
    • Yancun Liu
    • Songtao Shou
    • Yanfen Chai
  • View Affiliations

  • Published online on: February 24, 2021     https://doi.org/10.3892/mmr.2021.11941
  • Article Number: 302
  • Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.
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April-2021
Volume 23 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Gao Y, Wang C, Wang Z, Li W, Liu Y, Shou S and Chai Y: Semaphorin 3A contributes to sepsis‑induced immunosuppression by impairing CD4<sup>+</sup> T cell anergy. Mol Med Rep 23: 302, 2021
APA
Gao, Y., Wang, C., Wang, Z., Li, W., Liu, Y., Shou, S., & Chai, Y. (2021). Semaphorin 3A contributes to sepsis‑induced immunosuppression by impairing CD4<sup>+</sup> T cell anergy. Molecular Medicine Reports, 23, 302. https://doi.org/10.3892/mmr.2021.11941
MLA
Gao, Y., Wang, C., Wang, Z., Li, W., Liu, Y., Shou, S., Chai, Y."Semaphorin 3A contributes to sepsis‑induced immunosuppression by impairing CD4<sup>+</sup> T cell anergy". Molecular Medicine Reports 23.4 (2021): 302.
Chicago
Gao, Y., Wang, C., Wang, Z., Li, W., Liu, Y., Shou, S., Chai, Y."Semaphorin 3A contributes to sepsis‑induced immunosuppression by impairing CD4<sup>+</sup> T cell anergy". Molecular Medicine Reports 23, no. 4 (2021): 302. https://doi.org/10.3892/mmr.2021.11941