- by Minkyu LeeTissue-resident stem cells play an essential role in repairing barrier tissues subjected to frequent insults. However, the local cues that coordinate successful barrier repair or lead to tissue remodeling are largely unknown. Here we use murine models of airway injury, fate mapping, and null strains to identify a role for rare tuft epithelial cells in […]
- by Hiroaki HayashiCONCLUSION: Adherent platelets rapidly upregulate IL-33-expressing Macs, and platelet-derived LTC(4) sustains IL-33-driven expansion of AT2 cells and group 2 innate lymphoid cells, driving sex-biased amplification of T2I. This platelet-Mac axis may contribute to sex differences in type 2 inflammatory airway diseases such as asthma.
- by Jun NagaiCysteinyl leukotrienes (cysLTs) promote type 2 inflammation (T2I) by signaling through the type 1 and 3 cysLT-specific G protein-coupled receptors (GPCRs) (CysLT(1)R and CysLT(3)R). The type 2 cysteinyl leukotriene receptor (CysLT(2)R) can either promote or protect from T2I in vivo. The anti-inflammatory effects of CysLT(2)R are poorly understood. We find that prolonged CysLT(2)R signaling induces […]
- by Radomir KratchmarovType 2 inflammation unfolds over time and is coordinated by remarkably durable CD4+ Th2 cell responses, standing in contrast to the collapse of adaptive immunity seen in chronic infection and malignancy. In experimental models, short-lived Th2 effector cells and type 2 innate lymphocytes (ILC2) contribute to acute type 2 inflammation, yet the cellular architecture that […]
- by Airi NishidaPlatelets amplify type 2 inflammation (T2I) through incompletely understood mechanisms. Depletion of platelets markedly attenuated mast cell (MC) activation in a model of aspirin exacerbated respiratory disease (AERD) that depends on IL-33 and cysteinyl leukotrienes (cysLTs). We demonstrate an IL-33-driven feed-forward loop between platelets and MCs. IL-33 neutralization prevented increases in cysLTs and CXCL7, a […]
- by Régis JouliaDetermining spatial location of cells within tissues gives vital insight into the interactions between resident and inflammatory cells and is a critical factor for uncoupling the mechanisms driving disease. Here, we apply single-cell spatial transcriptomics to reveal the airway wall landscape in health and during asthma. We identified proinflammatory cellular ecosystems that exist within discrete […]
- by Joshua A BoyceStudies using mouse models of airway disease have advanced our understanding of the mechanisms driving eosinophilic airway inflammation and demonstrated potential therapeutic targets in asthma.
- by Ayobami AkenroyeOver the past 2 decades, mechanistic studies of allergic and type 2 (T2)-mediated airway inflammation have led to multiple approved therapies for the treatment of moderate-to-severe asthma. The approval and availability of these monoclonal antibodies targeting IgE, a T2 cytokine (IL-5) and/or cytokine receptors (IL-5Rα, IL-4Rα) has been central to the progresses made in the […]
- by Tahereh DerakhshanMast cells (MCs) expressing a distinctive protease phenotype (MCTs) selectively expand within the epithelium of human mucosal tissues during type 2 (T2) inflammation. While MCTs are phenotypically distinct from subepithelial MCs (MCTCs), signals driving human MCT differentiation and this subset's contribution to inflammation remain unexplored. Here, we have identified TGF-β as a key driver of […]
- by Minkyu LeeThe cysteinyl leukotrienes (CysLTs), LTC(4), LTD(4), and LTE(4), are potent lipid mediators derived from arachidonic acid through the 5-lipoxygenase pathway. These mediators produce both inflammation and bronchoconstriction through three distinct G protein-coupled receptors (GPCRs)-CysLT(1), CysLT(2), and OXGR1 (also known as CysLT(3) or GPR99). While CysLT-mediated functions in the effector phase of allergic inflammation and asthma […]
