# Combined single-cell transcriptome and immune repertoire analysis reveals hepatic and renal immune injury by heat stroke

## TL;DR

This study explores immune responses in heat stroke patients, revealing key immune cells and pathways linked to liver and kidney injury.

## Contribution

The study identifies novel peripheral immune signatures and highlights the NLRP3 inflammasome as a potential therapeutic target for heat stroke.

## Key findings

- Granzyme-positive T cells and CD56dim NK cells with high cytotoxicity are enriched in heat stroke patients.
- IL-1B+NLRP3+ monocytes with high inflammation and pyroptosis scores are associated with heat stroke.
- Blocking the NLRP3 inflammasome pathway may reduce organ injury in heat stroke.

## Abstract

Heat stroke (HS) is the most severe heat-related emergency, and its pathophysiology remains largely unknown, especially for exertional HS (EHS), which affects younger populations, athletes, and manual workers. Herein, we performed single-cell-transcriptomics, T cell receptor sequencing, and flow cytometry of PBMCs from 9 healthy control participants, 9 patients with heat exhaustion, and 9 patients with EHS to explore complex immunological responses associated with HS pathobiology. We showcased that granzyme-positive T cells and CD56dim NK cells with high cytotoxicity features and IL-1B+NLRP3+ monocytes with high inflammation and pyroptosis scores were enriched in HS, while the CD161+ T cells with innate immune-like, low cytotoxicity, and clonal expansion features were reduced in HS. Importantly, elevated granzyme-positive T and NK cells might interact with monocytes to induce pyroptosis of hepatic and renal cells and target organ injuries, and blocking the NLRP3 inflammasome pathway prior to the induction could alleviate organ injury in HS. This study offers deeper insights into the pathogenesis of HS, supporting the development of optimal treatment strategies.

This study provides with novel peripheral immune signitures of patients with heatstroke, identifying NLRP3 as novel intervention targets for treatment.