Search bioRxiv⌕ Search

Biology subjects

Babu, V. S.

Publications and source records attributed to Babu, V. S..

2 recordsLinked to original sources

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↗

Stress Combinations and their Interactions inPlants Database (SCIPDb): A one-stop resource for understanding combined stress responses in plants

We have developed Stress Combinations and their Interactions in Plants Database (SCIPDb; http://www.nipgr.ac.in/scipdb.php), a compendium and interactive platform offering information on both morpho-physio-biochemical (phenome) and molecular (transcriptome) responses of plants to different combinations of stresses. To delineate the effects of various stress combinations/categories on yield in major agricultural crops, global phenome data from 939 studies was analyzed and results showed that yield was affected to the greatest extent under the abiotic-abiotic stress category, followed by the biotic-biotic and abiotic-biotic stress categories. In the abiotic-abiotic stress category, drought-heat, heat-salinity, and ozone-UV are the major stress combinations causing high yield loss in barley, wheat, soybean, and quinoa crops. In the abiotic-biotic stress category, the salinity-weed stress combination causes highest yield loss in rice crop. In the biotic-biotic stress category, the nematode-fungus combination was most detrimental, causing considerable yield losses in potato, groundnut, and sugar beet crops. Transcriptome datasets from 36 studies hosted in SCIPDb identified novel genes. Thus far, these genes have not been known to play a role in combined stress. Integretome analysis under combined drought-heat stress pinpointed carbohydrate, amino acid, and energy metabolism pathways as the crucial metabolic, proteomic, and transcriptional components in plant tolerance to combined stress. These examples illustrate the application of SCIPDb in identifying novel genes and pathways involved in combined stress tolerance. Further, we showed the application of this database in identifying novel candidate genes and pathways for combined drought and pathogen stress tolerance in Arabidopsis and chickpea. To our knowledge, SCIPDb is the only publicly available platform that provides extensive information and paves the way for advancing mechanistic understanding of plant responses to combined stresses.

plant biology↗