Biology subjects

Praveen, M.

Publications and source records attributed to Praveen, M..

2 recordsLinked to original sources

bioRxiv2025

Attenuated adenosine mediated immune-dampening increases natural killer cell activity in early age-related macular degeneration

Non-exudative age-related macular degeneration (AMD) involves retinal pigment epithelium (RPE) dysfunction and has been linked to altered intraocular immunity. Our investigation focuses on immune cell subsets and inflammation-associated factors in the eyes with early and intermediate AMD. We observed elevated levels of activated natural killer (NK) cells and interferon-{gamma}, concurrent with reduced myeloid-derived suppressor cells (MDSCs) and adenosine in AMD eyes. Aqueous humor from AMD patients had diminished ability to dampen NK cell activation, an effect rescued by adenosine supplementation. The Cryba1 cKO mouse model recapitulated these immune alterations, and single-cell RNA-sequencing identified NK cell-related genes and NK cell-RPE interactions. Co-culture of activated NK cells with RPE cells induced barrier dysfunction and Gasdermin-E driven pyroptosis providing a functional link relevant to AMD. These findings suggest a double-hit model where elevated immune activation and loss of immune dampening mechanisms drive AMD progression. Resetting the intraocular immune balance may be a promising therapeutic strategy for managing early and intermediate AMD. O_FIG O_LINKSMALLFIG WIDTH=198 HEIGHT=200 SRC="FIGDIR/small/634301v2_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@1516bfaorg.highwire.dtl.DTLVardef@87f505org.highwire.dtl.DTLVardef@1e725caorg.highwire.dtl.DTLVardef@622717_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstractC_FLOATNO Illustra tion of pro posed mechanism underlying NK cell-RPE interaction in early AMD pathogenesis. Dysregulated NK cell communicate s with stressed RPE in early AMD immunopathology. Aberrant AMD aqueous humor and retina shows increased NK cells and NK effector molecules like IFN{gamma} with reduced MDSC and adenosine in human subjects, don or eye and animal model. Activated NK cells interaction with RPE causes dysfunction and pyroptotic cell death via Gasdermin-E pathway in AMD.. Created with BioRender.com C_FIG

immunology↗

bioRxiv2024

Paired transcriptomic analyses of atheromatous and control vessels reveal novel autophagy and immunoregulatory genes in peripheral artery disease

AbstractO_ST_ABSBackgroundC_ST_ABSPeripheral artery disease (PAD), a significant health burden worldwide, affects lower extremities due to atherosclerotic changes in the peripheral vessels. Although mechanisms of PAD have been studied, the molecular milieu of the plaques localized within peripheral arteries in patients are not well understood. Thus, to identify PAD lesion specific gene expression profiles precluding genetic, environmental and dietary biases, we studied the transcriptomic profile of plaque tissues normalized to non-plaque tissues from the same donors. MethodsTranscriptomic analysis of 9 paired samples of PAD patients from south Indian population was performed with institutional ethics approval and written consent. Plaque tissues were histologically confirmed. Expression of a select target gene set was done by qPCR from the same tissues. Bioinformatic and network analyses were performed using various statistical tools. ResultsA total of 296 upregulated, 274 downregulated genes and 186 non-coding RNAs were identified. STAG1, SPCC3, FOXQ1 and E2F3 were key downregulated genes and CD93 was top upregulated gene. Autophagosome assembly, cellular response to UV, cytoskeletal organization, TCR signaling and phosphatase activity were key dysregulated pathways identified in the study. Telomerase regulation and autophagy were identified as novel interacting pathways using network analysis. Plaque tissue was predominantly composed of immune cells and dedifferentiated cell populations indicated by cell specific marker imputed gene expression analysis. ConclusionThe current study identifies novel genes, non-coding RNAs, associated regulatory pathways and cell composition of the plaque tissue in PAD patients. The autophagy and immunoregulatory genes may drive novel mechanisms resulting in atheroma. These novel interacting networks and genes have the potential for PAD specific therapeutic applications.

molecular biology↗