TY - JOUR
T1 - Induction of a distinct macrophage population and protection from lung injury and fibrosis by Notch2 blockade
AU - Cruz Tleugabulova, Mayra
AU - Melo, Sandra P.
AU - Wong, Aaron
AU - Arlantico, Alexander
AU - Liu, Meizi
AU - Webster, Joshua D.
AU - Lau, Julia
AU - Lechner, Antonie
AU - Corak, Basak
AU - Hodgins, Jonathan J.
AU - Garlapati, Venkata S.
AU - De Simone, Marco
AU - Korin, Ben
AU - Avraham, Shimrit
AU - Lund, Jessica
AU - Jeet, Surinder
AU - Reiss, Alexander
AU - Bender, Hannah
AU - Austin, Cary D.
AU - Darmanis, Spyros
AU - Modrusan, Zora
AU - Brightbill, Hans
AU - Durinck, Steffen
AU - Diamond, Michael S.
AU - Schneider, Christoph
AU - Shaw, Andrey S.
AU - Nitschké, Maximilian
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - Macrophages are pleiotropic and diverse cells that populate all tissues of the body. Besides tissue-specific resident macrophages such as alveolar macrophages, Kupffer cells, and microglia, multiple organs harbor at least two subtypes of other resident macrophages at steady state. During certain circumstances, like tissue insult, additional subtypes of macrophages are recruited to the tissue from the monocyte pool. Previously, a recruited macrophage population marked by expression of Spp1, Cd9, Gpnmb, Fabp5, and Trem2, has been described in several models of organ injury and cancer, and has been linked to fibrosis in mice and humans. Here, we show that Notch2 blockade, given systemically or locally, leads to an increase in this putative pro-fibrotic macrophage in the lung and that this macrophage state can only be adopted by monocytically derived cells and not resident alveolar macrophages. Using a bleomycin and COVID-19 model of lung injury and fibrosis, we find that the expansion of these macrophages before lung injury does not promote fibrosis but rather appears to ameliorate it. This suggests that these damage-associated macrophages are not, by themselves, drivers of fibrosis in the lung.
AB - Macrophages are pleiotropic and diverse cells that populate all tissues of the body. Besides tissue-specific resident macrophages such as alveolar macrophages, Kupffer cells, and microglia, multiple organs harbor at least two subtypes of other resident macrophages at steady state. During certain circumstances, like tissue insult, additional subtypes of macrophages are recruited to the tissue from the monocyte pool. Previously, a recruited macrophage population marked by expression of Spp1, Cd9, Gpnmb, Fabp5, and Trem2, has been described in several models of organ injury and cancer, and has been linked to fibrosis in mice and humans. Here, we show that Notch2 blockade, given systemically or locally, leads to an increase in this putative pro-fibrotic macrophage in the lung and that this macrophage state can only be adopted by monocytically derived cells and not resident alveolar macrophages. Using a bleomycin and COVID-19 model of lung injury and fibrosis, we find that the expansion of these macrophages before lung injury does not promote fibrosis but rather appears to ameliorate it. This suggests that these damage-associated macrophages are not, by themselves, drivers of fibrosis in the lung.
UR - http://www.scopus.com/inward/record.url?scp=85208688538&partnerID=8YFLogxK
U2 - 10.1038/s41467-024-53700-9
DO - 10.1038/s41467-024-53700-9
M3 - Article
C2 - 39505846
AN - SCOPUS:85208688538
SN - 2041-1723
VL - 15
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 9575
ER -