Gut-derived memory γδ T17 cells exacerbate sepsis-induced acute lung injury in mice.

Xie, Bing; Wang, Mengyuan; Zhang, Xinyu; Zhang, Yujing; Qi, Hong; Liu, Hong; Wu, Yuming; Wen, Xiaoyue et al. · Nat Commun · 2024

basic_science · Level V

Where this comes from

Abstract

Sepsis is a critical global health concern linked to high mortality rates, often due to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). While the gut-lung axis involvement in ALI is recognized, direct migration of gut immune cells to the lung remains unclear. Our study reveals sepsis-induced migration of γδ T17 cells from the small intestine to the lung, triggering an IL-17A-dominated inflammatory response in mice. Wnt signaling activation in alveolar macrophages drives CCL1 upregulation, facilitating γδ T17 cell migration. CD44<sup>+</sup> Ly6C<sup>-</sup> IL-7R<sup>high</sup> CD8<sup>low</sup> cells are the primary migratory subtype exacerbating ALI. Esketamine attenuates ALI by inhibiting pulmonary Wnt/β-catenin signaling-mediated migration. This work underscores the pivotal role of direct gut-to-lung memory γδ T17 cell migration in septic ALI and clarifies the importance of localized IL-17A elevation in the lung.

Medical subject headings