Dataset Information

Effect of hypoxia and treatment with cyclosporine A on chemotaxis of RAMOS B cells

ABSTRACT: 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): B Cell, Cell Culture

SUBMITTER: Mukta Palshikar

LAB HEAD: Juilee Thakar

PROVIDER: PXD037004 | Pride | 2023-07-20

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	Hilchey_RAMOS-A_18-068.raw	Raw
	Hilchey_RAMOS-B_18-068.raw	Raw
	Hilchey_RAMOS-C_18-068.raw	Raw
	Hilchey_RAMOS-D_18-068.raw	Raw
	Hilchey_RAMOS-E_18-068.raw	Raw

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Publications

Executable Network Models of Integrated Multiomics Data.

Palshikar Mukta G MG Min Xiaojun X Crystal Alexander A Meng Jiayue J Hilchey Shannon P SP Zand Martin S MS Thakar Juilee J

Journal of proteome research 20230331 5

Multiomics profiling provides a holistic picture of a condition being examined and captures the complexity of signaling events, beginning from the original cause (environmental or genetic), to downstream functional changes at multiple molecular layers. Pathway enrichment analysis has been used with multiomics data sets to characterize signaling mechanisms. However, technical and biological variability between these layered data limit an integrative computational analyses. We present a Boolean ne ...[more]

PMID: 37000949

Publication: 1/2

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