PXD027357

PXD027357 is an original dataset announced via ProteomeXchange.

Title	Impaired M2 macrophage polarization in aging shifts the lipidome to pro-inflammatory mediators driving chronic inflammation and impairing tissue maintenance
Description	Inflammation is the natural defensive response of the immune system to an injury or infection and is regulated by small molecule mediators triggering different phases of the inflammatory process. In particular, lipid mediators (LM) and cytokines exhibit crucial regulatory functions in the progression and resolution of inflammation. Macrophages play a central role in this process and can adopt distinct phenotypes with specialized functions depending on their microenvironment: inflammatory M1 macrophages drive inflammation by the release of pro-inflammatory cytokines and LMs, like prostaglandins (PG) and leukotrienes (LT), while resolving M2 macrophages promote inflammation resolution and tissue regeneration by production of anti-inflammatory cytokines and specialized pro resolving mediators (SPM). Aging is associated with chronic and unresolved, low-grade inflammation (“inflammaging”) and aging-related dysfunction of macrophages in the resolution of inflammation and tissue maintenance has been reported. Yet, the underlying molecular mechanisms and functional consequences of latter processes remain poorly understood. Here, we show that polarization of peritoneal macrophages (PM) from geriatric mice towards an M2-like phenotype is impaired versus adult mice, resulting in aberrant LM formation and cytokine release. In PMs isolated from adult mice (PM-A) we observed a shift in LM formation from PGs and LTs to SPMs already after 4 h of polarization towards M2 with interleukin (IL) 4. In contrast, PMs from geriatric mice (PM-G) produced mainly LTs and PGs upon polarization. This pattern persists over the course of 48 h of polarization. Proteomic profiling revealed that polarization of PM A towards M2 yields a more distinct phenotype, clearly separated from M1, when compared to PM-G. We observed similar aging-related changes in the lipidome and cytokine profile of spleen, lung and liver tissue from mice. Hence, we hypothesize that during aging macrophage polarization towards M2 is impaired, which in turn drives chronic inflammation and disturbs tissue maintenance. By combining state-of-the art lipidomic and proteomic profiling we aim to uncover new molecular targets for pharmaceutical interventions to improve therapeutic strategies for elderly patients with chronic inflammatory diseases.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:11:41.730.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Emilio Cirri
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2021-07-16 03:54:35	ID requested
1	2023-10-24 13:15:54	announced
⏵ 2	2023-11-14 09:11:52	announced	2023-11-14: Updated project metadata.

Sch, ä, del P, Czapka A, Gebert N, Jacobsen ID, Ori A, Werz O, Metabololipidomic and proteomic profiling reveals aberrant macrophage activation and interrelated immunomodulatory mediator release during aging. Aging Cell, 22(7):e13856(2023) [pubmed]

submitter keyword: immune system,macrophages, differentiation, mouse, aging

Alessandro Ori
contact affiliation	Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) Beutenbergstraße 11 07745 Jena, Germany
contact email	Alessandro.Ori@leibniz-fli.de
lab head
Emilio Cirri
contact affiliation	Leibniz Institute on Ageing Fritz Lipmann Institute Jena
contact email	emilio.cirri@fli-leibniz.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/10/PXD027357

PRIDE project URI

• PRIDE
  1. PXD027357
     1. Label: PRIDE project
     2. Name: Impaired M2 macrophage polarization in aging shifts the lipidome to pro-inflammatory mediators driving chronic inflammation and impairing tissue maintenance