Investigating the role of visceral pleural macrophages in lung immune homeostasis
2Lydia Becker Institute of Immunology and Inflammation, University of Manchester
3Institute of Physiology, University of Zurich
Macrophages are crucial cells in maintaining pulmonary health. Specifically, the lung has been shown to harbour alveolar macrophages and multiple phenotypically distinct interstitial macrophage populations. Functional dissection of these cells is central to understanding macrophage contributions to lung health and disease. Here, using a novel murine binary splitCre model that relies on overlapping promoter activities of the Cx3cr1 and Lyve1 genes (Kim et al., 2021), we discovered a distinct macrophage population that resides in the visceral pleura of the lung. These cells, which we term visceral pleura macrophages (VPM), show a distinct expression profile from other pulmonary macrophage populations suggesting their involvement in VP maintenance. VPM also display prominent MHC II expression suggesting that VPM interact with T cells. To directly test the antigen presentation function of this macrophage population, targeted ablation of MHCII on VPM was performed. Mice with MHCII-deficient VPM (mutants) displayed a significant reduction of lung-resident CD4+ Foxp3+ ST2+ regulatory cells (ST2+ Tregs). Treg impairment was associated with an exhaustive CD8+ T cell phenotype, exclusively in the lung of aging mutant mice, indicative of altered immune homeostasis. Importantly, the disrupted VPM-Treg communication was impinged on the course of pulmonary protective immunity. Thus, influenza-infected mice showed impaired resolution and changes in their corresponding immune cell composition. Collectively, VPM, orchestrate immune homeostasis and protective responses within the lung, particularly in the context of infectious diseases. The in-depth characterisation of VPM and their crosstalk with Treg cell populations might open new avenues for modulating pulmonary immunity.