| First Author | Nascimento M | Year | 2023 |
| Journal | Front Immunol | Volume | 14 |
| Pages | 1224383 | PubMed ID | 38146368 |
| Mgi Jnum | J:348229 | Mgi Id | MGI:7569542 |
| Doi | 10.3389/fimmu.2023.1224383 | Citation | Nascimento M, et al. (2023) NLRP6 controls pulmonary inflammation from cigarette smoke in a gut microbiota-dependent manner. Front Immunol 14:1224383 |
| abstractText | 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 Nlrp6-deficient 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 inflammasome-dependent 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 Nlrp6-deficient mice to WT mice decreased airway lung inflammation in WT mice, highlighting an NLRP6-dependent gut-to-lung axis controlling pulmonary inflammation. |
