Notch signaling pathway regulates T cell dysfunction in septic patients.

Notch signaling pathway regulates T cell dysfunction in septic patients. Int Immunopharmacol. 2019 Sep 13;76:105907 Authors: Jin B, Liang Y, Liu Y, Zhang LX, Xi FY, Wu WJ, Li Y, Liu GH Abstract Sepsis disrupts innate and adaptive immune response, and immune disorders may also impact clinical course of sepsis. Notch signaling pathway plays a vital role in T cell modulation and differentiation. The aim of current study was to investigate the immunoregulatory function of Notch signaling pathway to T cells in patients with sepsis and septic shock. Twenty-seven sepsis patients, twenty-five septic shock patients, and twenty-one normal controls (NCs) were enrolled. Notch receptors mRNA levels were semi-quantified by real-time PCR. The absolute numbers of CD3+, CD4+, and CD8+ T cells were measured by flow cytometry. Key transcriptional factors of CD4+ T cells, cytotoxic molecules in CD8+ T cells, and cytotoxicity of CD8+ T cells were investigated. The regulatory activities of Notch signaling inhibition by γ-secretase inhibitor (GSI) on purified CD4+ and CD8+ T cells from sepsis and septic shock patients were also assessed. Notch1 mRNA relative level was significantly elevated in sepsis and septic shock patients when compared with NCs. CD4+ and CD8+ T cells were dysfunctional in sepsis and septic shock, which presented as decreased cell accounts, down-regulation of Th1/Th17 transcriptional factors and cytotoxic molecules (perforin, granzyme ...
Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Tags: Int Immunopharmacol Source Type: research