Selected Publication:

SHR Neuro Cancer Cardio Lipid Metab Microb

Hochgerner, M; Jiang, Y; Sun, S; Huang, F; Marsh, LM; Lin, X; Tang, X.
Loss of ALK3 Ameliorates Acute but Aggravates Chronic Lung Inflammation In Vivo.
Immunology. 2025; Doi: 10.1111/imm.13957
Web of Science PubMed FullText FullText_MUG

 

Co-authors Med Uni Graz

Marsh Leigh

Altmetrics:

Dimensions Citations:

Plum Analytics:

Scite (citation analytics):

Abstract:

ALK3 (BMPR1a) is a type-1 receptor of the TGF-β receptor superfamily. It translates signals mainly from bone morphogenetic proteins, but also from TGF-β1. Previously, we showed that specific deletion of ALK3 in antigen-presenting cells (APCs) led to increased inflammation in the skin. It is unknown whether the regulation of ALK3 in APCs is specific to the skin or generally involved in multiple tissues. Therefore, we investigated the role of ALK3 in APCs in the lung. We used mice with a specific deletion of ALK3 under the CD11c promoter as well as pharmacological blockade of ALK3-signalling with DMH-1 in vivo in Bleomycin- and LPS-induced lung inflammation, as well as follow-up in vitro experiments. Lung inflammation was analysed via histology, flow cytometry and single-cell-RNA-sequencing. Deletion or blockade of ALK3 aggravated Bleomycin-induced and long-term LPS-induced lung inflammation. Interestingly, acute LPS-induced lung inflammation was ameliorated. ALK3 blockade did not reduce recruitment of immune cells to the lung but changed gene expression in neutrophils, downregulating inflammation-associated genes. In vitro, DMH-1 did not directly affect neutrophils but did affect DCs, macrophages and AT-2 cells. The aggravation of longer-lasting lung inflammation matches our previous data from the skin, down to reduced numbers of T_REG. Unexpectedly, that same loss/blockade of ALK3 ameliorates acute lung inflammation. Our results suggest that ALK3 is an important receptor in APCs, enhancing their ability to activate a fast, neutrophilic inflammation as well as to counteract longer-lasting inflammations. Thus, ALK3 has (at least) two different functions at different stages of inflammation. With deeper understanding, ALK3 could be an important target for modulating acute and chronic lung inflammation.

Find related publications in this database (Keywords)

ALK3

antigen-presenting cells

BMPR1a

dendritic cells

lung

macrophages

neutrophils

© Med Uni Graz • Imprint