CD45 alleviates airway inflammation and lung fibrosis by limiting expansion and activation of ILC2s
Cui G et al.
Proc Natl Acad Sci U S A, 2023
Type 2 innate lymphoid cells (ILC2s) are essential for immune responses against parasitic infections and tissue homeostasis and are involved in the pathogenesis of allergic and inflammatory diseases. Although a variety of molecules that positively regulate ILC2 development and activation have been extensively studied, the factors that limit their cell population size and response remain understudied. In this study, the researchers found that CD45, a membrane-bound tyrosine phosphatase essential for T-cell development, negatively regulates ILC2s in a cell-intrinsic manner. ILC2s from CD45-deficient mice showed increased proliferation and maturation in the bone marrow, and in the lungs showed an overactivated phenotype with high glycolytic capacity. In addition, CD45 signaling inhibited the type 2 inflammatory response of lung ILC2s, attenuating airway inflammation and lung fibrosis. Finally, interaction with galectin-9 affected CD45 signaling in ILC2s. These results suggest that CD45 is a cell-intrinsic negative regulator of ILC2s and prevents lung inflammation and fibrosis through ILC2s.DOI: 10.1073/pnas.2215941120
Airway-Associated Macrophages in Homeostasis and Repair![]()
Engler AE et al.
Cell Rep, 2020
The heterogeneity of the myeloid lineage spectrum in the lung is increasingly recognized, but little is known about the cell populations that are specifically associated with the airways. In this study, the researchers used single-cell RNA sequencing, flow cytometry and immunofluorescence to characterize myeloid lineage cells during homeostasis and epithelial injury/repair in mouse airways. The authors identified submucosal macrophages (like lung interstitial macrophages) and intraepithelial macrophages. Early neutrophils and submucosal macrophages increased after injury, including M2-like macrophages. Intraepithelial macrophages were lost after injury and subsequently restored by CCR2+ monocytes. The authors found that tracheal epithelial repair was impaired in Ccr2-deficient mice. Mast cells and type 2 innate lymphoid cells are the source of IL-13, which polarizes macrophages and directly affects basal cell behavior. Their proximity to the airway epithelium makes these myeloid cell populations potential therapeutic targets for airway disease.DOI: 10.1016/j.celrep.2020.108553.
Editor & Reviewer: Yanwen Wang
