PXD028390

PXD028390 is an original dataset announced via ProteomeXchange.

Title	Proteomic phenotyping of stimulated Müller cells uncovers profound pro-inflammatory signaling and antigen-presenting capacity
Description	Müller cells are the main macroglial cells of the retina exerting a wealth of functions to maintain retinal homoeostasis. Upon pathological changes in the retina, they become gliotic with both protective and detrimental consequences. Accumulating data also provide evidence for a pivotal role of Müller cells in the pathogenesis of diabetic retinopathy (DR). While microglial cells, the resident immune cells of the retina are considered as main players in inflammatory processes associated with DR, the implication of activated Müller cells in chronic retinal inflammation remains to be elucidated. In order to assess the signaling capacity of Müller cells and their role in retinal inflammation, we performed in-depth proteomic analysis of Müller cell proteomes and secretomes after stimulation with INFγ, TNFα, IL-4, IL-6, IL-10, TGFβ1, TGFβ2 and TGFβ3. We used both, primary porcine Müller cells and the human Müller cell line MIO-M1 for our hypothesis generating approach. Our results point towards an intense signaling capacity of Müller cells, which reacted in a highly discriminating manner upon treatment with different cytokines. Stimulation of Müller cells results in a primarily pro-inflammatory phenotype with secretion of cytokines and components of the complement system. Furthermore, we observed evidence for mitochondrial dysfunction, implying oxidative stress after treatment with the various cytokines. Finally, both MIO-M1 cells and primary porcine Müller cells showed several characteristics of atypical antigen-presenting cells, as they are capable of inducing MHC class I and MHC class II with co-stimulatory molecules. In line with this, they express proteins associated with formation and maturation of phagosomes. Thus, our findings underline the importance of Müller cell signaling in the inflamed retina, indicating an active role in chronic retinal inflammation underlying the pathogenesis of diabetic retinopathy.
HostingRepository	PRIDE
AnnounceDate	2022-02-16
AnnouncementXML	Submission_2022-02-16_08:33:35.200.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Stefanie Hauck
SpeciesList	scientific name: Sus scrofa domesticus (domestic pig); NCBI TaxID: 9825; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-09-09 08:34:57	ID requested
⏵ 1	2022-02-16 08:33:36	announced

Schmalen A, Lorenz L, Grosche A, Pauly D, Deeg CA, Hauck SM, ller Cells Uncovers Profound Pro-Inflammatory Signaling and Antigen-Presenting Capacity. Front Pharmacol, 12():771571(2021) [pubmed]

submitter keyword: Müller cells, atypical antigen-presenting cell, immune response, diabetic retinopathy, pro-inflammatory, complement system, cytokines. retina

Stefanie M. Hauck
contact affiliation	1Research Unit Protein Science and Metabolomics and Proteomics Core, Helmholtz Zentrum München, German Research Center for Environmental Health, D-85764 Neuherberg, Germany
contact email	hauck@helmholtz-muenchen.de
lab head
Stefanie Hauck
contact affiliation	Research Unit Protein Science, Helmholtz Zentrum München
contact email	hauck@helmholtz-muenchen.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD028390
     1. Label: PRIDE project
     2. Name: Proteomic phenotyping of stimulated Müller cells uncovers profound pro-inflammatory signaling and antigen-presenting capacity