PXD038390

PXD038390 is an original dataset announced via ProteomeXchange.

Title	ALOX12-expressing macrophages produce MCTRs to promote local efferocytosis and tissue repair
Description	Poor wound healing due to dysregulated tissue repair responses can exacerbate and prolong disease. Successful tissue repair is critically dependent on the timely clearance of apoptotic cells by macrophages in a process termed efferocytosis. Mechanisms and factors that link these two fundamental processes are therefore of great interest. Herein, we observed that a subset of 12-lipoxygenase (ALOX12)-expressing macrophages upregulate the production of host protective autacoids termed maresin conjugates in tissue regeneration (MCTR) during efferocytosis. MCTRs in turn play autocrine and paracrine functions in enhancing the ability of both ALOX12-positive and surrounding ALOX12-negative macrophages to uptake apoptotic cells. These effects of ALOX12-positive macrophages and MCTRs in regulating apoptotic cells clearance was also observed at sites of high apoptotic cell burden in mouse and flatworm models, as the formation of these mediators was upregulated and abrogation of related ALOX activity in mice reduced the ability of macrophages to clear apoptotic cells. Furthermore, add-back of MCTRs rapidly enhanced the efferocytosis capability of macrophages in mice and planarian flatworms. Mechanistic studies in macrophages revealed that MCTRs modulated Rac1 signalling and glycolytic metabolism, two pathways crucial for effective efferocytosis, and enhanced efferocytosis-induced WNT ligand production. Inhibition of Rac1 abrogated the ability of MCTRs to enhance glucose uptake and efferocytosis in vitro, while inhibiting either Rac1, glycolysis, or WNT ligand production prevented MCTR-mediated enhancement of apoptotic cell clearance and tissue regeneration. Taken together, our findings identify a central role for ALOX12-expressing macrophages in the regulation of efferocytosis and tissue repair via the local formation of MCTRs.
HostingRepository	PRIDE
AnnounceDate	2023-12-12
AnnouncementXML	Submission_2023-12-12_06:16:43.991.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD038390
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Vinothini Rajeeve
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-11-26 04:03:16	ID requested
⏵ 1	2023-12-12 06:16:44	announced

10.6019/PXD038390;

Koenis DS, de Matteis R, Rajeeve V, Cutillas P, Dalli J, Efferocyte-Derived MCTRs Metabolically Prime Macrophages for Continual Efferocytosis via Rac1-Mediated Activation of Glycolysis. Adv Sci (Weinh), 11(7):e2304690(2024) [pubmed]

10.1002/advs.202304690;

submitter keyword: ALOX12,Macrophages, phosphoproteomics, LC-MS/MS

Professor Pedro R. Cutillas
contact affiliation	Centre for Genomics and Computational Biology Barts Cancer Institute Queen Mary, University of London John Vane Science Centre, Charterhouse Square, London EC1M 6BQ
contact email	p.cutillas@qmul.ac.uk
lab head
Vinothini Rajeeve
contact affiliation	Centre for Haemato Oncology
contact email	v.rajeeve@qmul.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD038390
     1. Label: PRIDE project
     2. Name: ALOX12-expressing macrophages produce MCTRs to promote local efferocytosis and tissue repair