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

ABSTRACT

Background

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.

Method

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.

Results

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.

Conclusions

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.

KEYWORDS:

• CD4⁺ T cells
• IL1 receptor accessory protein
• sepsis

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authors’ contributions

LH and CRW participated in the design of this study, and they both performed the statistical analysis. DX and YHC carried out the study and collected important background information. JGT drafted the manuscript. All authors read and approved the final manuscript.

Additional information

Funding

This study was funded by Minhang District Natural Science Research (2022MHZ068).