biostudies-literatureBaßler KNIAID NIH HHSNIMH NIH HHSNCI NIH HHS917232https://www.ebi.ac.uk/biostudies/studies/S-EPMC9377018biostudies-literatureUnknown13Despite its high prevalence, the cellular and molecular mechanisms of chronic obstructive pulmonary disease (COPD) are far from being understood. Here, we determine disease-related changes in cellular and molecular compositions within the alveolar space and peripheral blood of a cohort of COPD patients and controls. Myeloid cells were the largest cellular compartment in the alveolar space with invading monocytes and proliferating macrophages elevated in COPD. Modeling cell-to-cell communication, signaling pathway usage, and transcription factor binding predicts TGF-β1 to be a major upstream regulator of transcriptional changes in alveolar macrophages of COPD patients. Functionally, macrophages in COPD showed reduced antigen presentation capacity, accumulation of cholesteryl ester, reduced Frontiers in immunologyAlveolar macrophages in early stage COPD show functional deviations with properties of impaired immune activation.PMC9377018U54 CA217377U24 AI118672U19 MH114821Dudkin ESkowasch DBecker MKohler MFerreira HJReiz BKnoll RHolsten LTheis FJThomas DBaum PSchultze JLKraut MBaßler KFujii WHandler KSchreiber TKaltheuner IHThiele CGeyer MReusch NWagner AGunther PHughes TKBeyer MHasenauer JDickten HLuecken MDHorne ADe Domenico ETheis HHinkley EKapellos TSAschenbrenner ACWadsworth MHOsei-Sarpong CSchulte-Schrepping JPizarro CKroger CWohnhaas CTYosef NBonaguro LShalek AKUlas TWarnat-Herresthal SFeißt ABaumgartner FfalseAlveolar macrophages in early stage COPD show functional deviations with properties of impaired immune activation.Despite its high prevalence, the cellular and molecular mechanisms of chronic obstructive pulmonary disease (COPD) are far from being understood. Here, we determine disease-related changes in cellular and molecular compositions within the alveolar space and peripheral blood of a cohort of COPD patients and controls. Myeloid cells were the largest cellular compartment in the alveolar space with invading monocytes and proliferating macrophages elevated in COPD. Modeling cell-to-cell communication, signaling pathway usage, and transcription factor binding predicts TGF-β1 to be a major upstream regulator of transcriptional changes in alveolar macrophages of COPD patients. Functionally, macrophages in COPD showed reduced antigen presentation capacity, accumulation of cholesteryl ester, reduced 2022-01-01T00:00:00Z20222026-04-08T11:08:07.122Z2025-02-19T04:38:25.695ZS-EPMC93770183597936410.3389/fimmu.2022.917232