IL1RAP Exacerbates Sepsis-Induced Pulmonary and Spleen Injury Through Regulating CD4+ T Lymphocyte Differentiation.

Complex pathophysiological the specific mechanism of sepsis on CD4⁺ T-cell responses is less well understood. IL1 receptor accessory protein (IL1RAP) was found to be involved in activating host immune responses. Cecum ligation and puncture (CLP) was utilized to build a mouse sepsis model. The experiment was randomly divided into four groups: Sham, CLP, CLP + shNC, and CLP + shIL1RAP group. qRT-PCR suggested mRNA levels of IL1RAP were decreased when IL1RAP was knocked down with the mRNA levels of IL-1β, NF-κB, and p38 decreased. Histopathology showed severe pathological damage with alveolar integrity lost, red blood cells in the alveoli, massive inflammatory cell infiltration, and the alveolar wall was thickening in the CLP group. The inflammatory cytokine levels of TNF-α, IL-1β, and IFN-γ were elevated in CLP mice by ELISA. The counts of CD4⁺ T cells were decreased in sepsis mice in peripheral blood, spleen, and BALF by flow cytometry. However, the above was blocked down when using shIL1RAP. Western blot suggested sh IL1RAP inhibited IL-1β, NF-κB, and p38 protein expressions. We defined IL1RAP as a new target gene through NF-κB/MAPK pathways regulating CD4⁺ T lymphocyte differentiation mediated the progression of sepsis, which is potentially exploitable for immunotherapy. [ABSTRACT FROM AUTHOR]