TY - JOUR
T1 - Alveolar macrophages in early stage COPD show functional deviations with properties of impaired immune activation
AU - Baßler, Kevin
AU - Fujii, Wataru
AU - Kapellos, Theodore S.
AU - Dudkin, Erika
AU - Reusch, Nico
AU - Horne, Ari
AU - Reiz, Benedikt
AU - Luecken, Malte D.
AU - Osei-Sarpong, Collins
AU - Warnat-Herresthal, Stefanie
AU - Bonaguro, Lorenzo
AU - Schulte-Schrepping, Jonas
AU - Wagner, Allon
AU - Günther, Patrick
AU - Pizarro, Carmen
AU - Schreiber, Tina
AU - Knoll, Rainer
AU - Holsten, Lisa
AU - Kröger, Charlotte
AU - De Domenico, Elena
AU - Becker, Matthias
AU - Händler, Kristian
AU - Wohnhaas, Christian T.
AU - Baumgartner, Florian
AU - Köhler, Meike
AU - Theis, Heidi
AU - Kraut, Michael
AU - Wadsworth, Marc H.
AU - Hughes, Travis K.
AU - Ferreira, Humberto J.
AU - Hinkley, Emily
AU - Kaltheuner, Ines H.
AU - Geyer, Matthias
AU - Thiele, Christoph
AU - Shalek, Alex K.
AU - Feißt, Andreas
AU - Thomas, Daniel
AU - Dickten, Henning
AU - Beyer, Marc
AU - Baum, Patrick
AU - Yosef, Nir
AU - Aschenbrenner, Anna C.
AU - Ulas, Thomas
AU - Hasenauer, Jan
AU - Theis, Fabian J.
AU - Skowasch, Dirk
AU - Schultze, Joachim L.
N1 - Publisher Copyright:
Copyright © 2022 Baßler, Fujii, Kapellos, Dudkin, Reusch, Horne, Reiz, Luecken, Osei-Sarpong, Warnat-Herresthal, Bonaguro, Schulte-Schrepping, Wagner, Günther, Pizarro, Schreiber, Knoll, Holsten, Kröger, De Domenico, Becker, Händler, Wohnhaas, Baumgartner, Köhler, Theis, Kraut, Wadsworth, Hughes, Ferreira, Hinkley, Kaltheuner, Geyer, Thiele, Shalek, Feißt, Thomas, Dickten, Beyer, Baum, Yosef, Aschenbrenner, Ulas, Hasenauer, Theis, Skowasch and Schultze.
PY - 2022/7/28
Y1 - 2022/7/28
N2 - 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 cellular chemotaxis, and mitochondrial dysfunction, reminiscent of impaired immune activation.
AB - 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 cellular chemotaxis, and mitochondrial dysfunction, reminiscent of impaired immune activation.
KW - TGF-β1
KW - blood
KW - bronchoalveolar lavage
KW - chronic obstructive pulmonary disease
KW - impaired immune activation
KW - macrophage
KW - monocyte
UR - http://www.scopus.com/inward/record.url?scp=85136078964&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2022.917232
DO - 10.3389/fimmu.2022.917232
M3 - Article
C2 - 35979364
AN - SCOPUS:85136078964
SN - 1664-3224
VL - 13
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 917232
ER -