Journal Article

NLRP6 controls pulmonary inflammation from cigarette smoke in a gut microbiota-dependent manner

Savigny, Florence, Straube, Marjolene, Ryffel, Bernhard, Couillin, Isabelle, Chamaillard, Mathias, Nascimento, Mégane, Apetoh, Lionel, Trovero, Fabrice, Gosset, Philippe, Gombault, Aurélie, Sokol, Harry, Huot-Marchand, Sarah, Le Bert, Marc, Quesniaux, Valérie F J, Riteau, Nicolas, Fanny, Manoussa, van Snick, Jacques

2023

Overview

Chronic obstructive pulmonary disease (COPD) is a major health issue primarily caused by cigarette smoke (CS) and characterized by breathlessness and repeated airway inflammation. NLRP6 is a cytosolic innate receptor controlling intestinal inflammation and orchestrating the colonic host-microbial interface. However, its roles in the lungs remain largely unexplored. Using CS exposure models, our data show that airway inflammation is strongly impaired in Nlrp6deficient mice with drastically fewer recruited neutrophils, a key cell subset in inflammation and COPD. We found that NLRP6 expression in lung epithelial cells is important to control airway and lung tissue inflammation in an inflammasomedependent manner. Since gut-derived metabolites regulate NLRP6 inflammasome activation in intestinal epithelial cells, we investigated the link between NLRP6, CS-driven lung inflammation, and gut microbiota composition. We report that acute CS exposure alters gut microbiota in both wild-type (WT) and Nlrp6-deficient mice and that antibiotic treatment decreases CS-induced lung inflammation. In addition, gut microbiota transfer from dysbiotic Nlrp6deficient mice to WT mice decreased airway lung inflammation in WT mice, h ighlighting an NLRP6-d epe nde nt gut-to-lu ng a xis co ntrolling pulmonary inflammation.

• Publisher: Frontiers
• Subject: Life Sciences