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Series GSE188356 Query DataSets for GSE188356
Status Public on Apr 30, 2023
Title Cholesterol homeostatic regulator SREBP2 promotes macrophage alternative activation and allergic airway inflammation
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Metabolic reprogramming is well-appreciated to be able to control macrophage activation. However, it remains unknown whether the SREBPs-lipogenesis pathway is involved in macrophage alternative (or M2) activation. Here, we showed that IL4-induced M2 activation was coupled with increased SREBP2 maturation and activated cholesterol biosynthetic pathway, while the SREBP1-fatty acid biosynthesis pathway remained unaffected after IL4 stimulation. Genetic or pharmacologic blockade of SREBP2 maturation significantly inhibited IL4-induced M2 activation independent of cholesterol. Instead, cholesterol inhibited M2 activation most likely through its feedback regulation of SREBP2 maturation. Mechanically, the upregulation of SREBP2 maturation was dependent on the activation of upstream MTOR, and mature SREBP2 increased the expression of KAZALD1 and subsequently activated the IGF1 signaling to promote IL4-induced M2 activation. Consistently, myeloid-specific Scap deficiency markedly decreased the number of M2 macrophages in the lung and attenuated the HDM-induced allergic airway inflammation. Taken together, these findings highlight a critical role for cholesterol homeostatic regulator SREBP2 in M2 activation, which advances our understanding of the regulation of immunometabolism for M2 activation and points to new opportunities for therapeutic control of M2 activation and allergic airway inflammation.
Overall design mRNA profiles of BMDM treated with IL4, IL4 + fatostatin, IL4 + betulin, IL4 + 25-HC, IL4 + PF429424, and IL4 + 1,10-Phen, respectively.
Contributor(s) Shen H, Chen Z, Li W, Wu Y
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Submission date Nov 07, 2021
Last update date May 02, 2023
Contact name Yinfang Wu
Organization name Zhejiang University
Street address Yuhangtang RD 866
City Hangzhou
ZIP/Postal code 310058
Country China
Platforms (1)
GPL28330 DNBSEQ-T7 (Mus musculus)
Samples (6)
GSM5678208 X1
GSM5678209 X2
GSM5678210 X3
BioProject PRJNA778525
SRA SRP344932

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Supplementary file Size Download File type/resource
GSE188356_RAW.tar 5.5 Mb (http)(custom) TAR (of CSV)
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Raw data are available in SRA
Processed data provided as supplementary file

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