PXD037004-4

PXD037004 is an original dataset announced via ProteomeXchange.

Title	Effect of hypoxia and treatment with cyclosporine A on chemotaxis of RAMOS B cells
Description	Background: Hypoxia is a potent molecular signal for cellular metabolism, mitochondrial function, and migration. Conditions of low oxygen tension trigger regulatory cascades mediated via the highly conserved HIF-1 α post-translational modification system. In the adaptive immune response, B cells (Bc) are activated and differentiate under hypoxic conditions within lymph node germinal centers, and subsequently migrate to other compartments. During migration, they traverse through changing oxygen levels, ranging from 1-5% in the lymph node to 5-13% in the peripheral blood. Interestingly, the calcineurin inhibitor cyclosporine A is known to stimulate prolyl hydroxylase activity, resulting in HIF-1 α destabilization and may alter Bc responses directly. Over 60% of patients taking calcineurin immunosuppressant medications have hypo-gammaglobulinemia and poor vaccine responses, putting them at high risk of infection with significantly increased morbidity and mortality. Results: We demonstrate that oxygen tension is a previously unrecognized Bc regulatory switch, altering CXCR4 and CXCR5 chemokine receptor signaling in activated Bc through HIF-1 α expression, and controlling critical aspects of Bc migration. Our data demonstrate that calcineurin inhibition hinders this oxygen regulatory switch in primary human Bc. Conclusion: This previously unrecognized effect of calcineurin inhibition directly on human Bc has significant and direct clinical implications.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:54:31.300.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mukta Palshikar
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-25 15:26:48	ID requested
1	2023-07-20 10:36:16	announced
2	2023-11-14 07:15:34	announced	2023-11-14: Updated project metadata.
3	2023-11-14 09:02:33	announced	2023-11-14: Updated project metadata.
⏵ 4	2024-10-22 05:54:32	announced	2024-10-22: Updated project metadata.

Hilchey SP, Palshikar MG, Emo JA, Li D, Garigen J, Wang J, Mendelson ES, Cipolla V, Thakar J, Zand MS, sensing, molecular switch. BMC Immunol, 21(1):13(2020) [pubmed]

10.1186/s12865-020-0342-8;

10.1021/acs.jproteome.2c00730;

Palshikar MG, Min X, Crystal A, Meng J, Hilchey SP, Zand MS, Thakar J, Executable Network Models of Integrated Multiomics Data. J Proteome Res, 22(5):1546-1556(2023) [pubmed]

submitter keyword: cyclosporine, hypoxia, HIF1A, immunosuppressant,B cells, CXCL12

Juilee Thakar
contact affiliation	Department of Microbiology and Immunology Department of Biomedical Genetics Department of Biostatistics and Computational Biology University of Rochester, Rochester, NY
contact email	juilee_thakar@urmc.rochester.edu
lab head
Mukta Palshikar
contact affiliation	University of Rochester
contact email	mukta_palshikar@urmc.rochester.edu
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/2023/07/PXD037004

PRIDE project URI

• PRIDE
  1. PXD037004
     1. Label: PRIDE project
     2. Name: Effect of hypoxia and treatment with cyclosporine A on chemotaxis of RAMOS B cells