Biology subjects

Raina, A.

Publications and source records attributed to Raina, A..

4 recordsLinked to original sources

bioRxiv2026

Distinct Programs of Tissue Adaptation Shape Vitreous CD4+ and CD8+ T-cell States in Chronic Uveitis

Tissue-resident memory (TRM) T-cells are increasingly recognized as key mediators of chronic autoimmune inflammation, yet their organization and functional adaptation within the eye remain poorly understood. We investigated paired vitreous body biopsies and peripheral blood T cells from patients with chronic posterior segment uveitis using multiparameter flow cytometry, antigen-specific stimulation assays, single-cell RNA sequencing, and T-cell receptor sequencing to define the intraocular tissue-adaptive immune states. Vitreous T cells were phenotypically, transcriptionally, and clonally distinct from their circulating counterparts and enriched for canonical TRM markers. However, tissue adaptation differed substantially between CD4+ and CD8+ lineages. Vitreous CD4+ T cells segregated into clonally expanded tissue-adaptive states characterized by greater CXCR6 expression, enhanced antigen-specific cytokine responses, and well-defined transcriptional profiles. In contrast, vitreous CD8+ T cells expressed higher levels of the retention-associated markers CD103 and CD49a yet maintained greater clonal and phenotypic continuity with peripheral blood T cells. Both vitreous CD4+ and CD8+ subsets exhibited a restrained effector profile associated with tissue-adaptive transcriptional programs. Our data reveal that CD4+ and CD8+ T cells in chronic uveitis assume distinct states in the vitreous microenvironment, such that the intraocular immune response relies on both localized tissue retention and active adaptation to the inflammatory niche.

immunology↗

bioRxiv2025

Distinct alpha-synuclein strains derived from Parkinson's disease patient tissues trigger differential inclusion pathology in a novel biosensor cell model

Background-Synuclein (Syn) can misfold and aggregate to form fibrillar {beta}-sheet-rich aggregates ("strains") that are phosphorylated (p-Syn) and deposited into intracellular inclusions in the brain, the pathological hallmark of synucleinopathies including Parkinsons disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Previously, we reported that seed amplification assays such as real-time quaking-induced conversion (RT-QuIC) amplifies and detects Syn strains from the patient skin. However, whether skin-derived Syn strains induce disease-specific pathological features in a biological system is unknown. MethodsWe generated a U251 human glioblastoma cell line expressing fluorescently tagged Syn carrying the PD-linked A53T mutation and Forster resonance energy transfer (FRET)-based U251 biosensor cells. Using fluorescence microscopy coupled with in situ detergent extraction, FRET-Flow cytometry and high-content confocal imaging, we examined the pathological burden and morphology of p-Syn inclusions seeded by RT-QuIC-amplified patient skin and brain Syn strains in Syn-expressing U251 cells, FRET-based Syn biosensor cells and Syn biosensor cell-derived neurons. ResultsU251 cells allow robust and rapid in situ detection of detergent-insoluble intracellular Syn inclusions triggered by exogenous Syn seeds. In U251 FRET-based biosensor cells, PD skin-amplified strains induce a greater pathological burden and distinct p-Syn inclusion morphology from PD brain-amplified and DLB skin-amplified strains. Inclusion morphology of DLB and MSA skin- and brain-amplified strains are comparable. Furthermore, skin-amplified Syn strains induce neuronal inclusions and cause degeneration of induced neurons reprogrammed from the U251 biosensor cells. Finally, biosensor cell-propagated PD skin Syn strains induce higher seeding activity measured by RT-QuIC than PD brain and DLB skin Syn strains, linking intracellular pathological burden to in vitro seeding activity. ConclusionsWe report the detection of distinct PD strains derived from patient skin and brain tissues that trigger unique pathological phenotypes in U251 Syn biosensor cells and cause degeneration of reprogrammed neurons from the same cell lineage. Moreover, DLB and MSA skin Syn strains mimic pathological features of their brain Syn strains in these biosensor cells. Therefore, the U251 Syn biosensor cell model is a robust tool to potentially discriminate PD and DLB synucleinopathies and to study Syn tissue- and strain-specific etiology and pathogenesis. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=97 SRC="FIGDIR/small/646513v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@acf0a5org.highwire.dtl.DTLVardef@1eb0d17org.highwire.dtl.DTLVardef@a89c75org.highwire.dtl.DTLVardef@1b7eca4_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2020

EGCG modulates nuclear formaldehyde-induced Tau phosphorylation in Neuronal cells

Tau hyperphosphorylation is one of the major causes of Alzheimers disease pathology. The abnormal phosphorylation curtails the physiological function of Tau of microtubule stabilization and renders it more prone to aggregation. Apart from its function in the cytoplasm, Tau is attributed to play a role in the nucleus. Nuclear function of Tau is dependent on its residue-specific phosphorylation. We studied the effect of a green tea polyphenol, EGCG, on the formaldehyde-induced Tau phosphorylation and Tau kinase CDK5. Interestingly, we observed unique localization of phospho-Tau (AT 8 and AT 100) in the nucleus in various EGCG treatments. EGCG was also found to lower the levels of CDK5 in the formaldehyde-treated cells. Further, the role of EGCG was tested in vivo in drosophila eye model of hyperphosphorylated Tau (Tau E14). The results suggest that EGCG can modulate nuclear Tau phosphorylation and lower the levels of Tau kinase CDK5.

cell biology↗

bioRxiv2019

A role of cellular translation regulation associated with toxic Huntingtin protein

Huntingtons disease (HD) is a severe neurodegenerative disorder caused by poly Q repeat expansion in the Huntingtin (Htt) gene. While the Htt amyloid aggregates are known to affect many cellular processes, its role in translation is not addressed. Here we report pathogenic Htt expression causes protein synthesis deficit in cells. We find a functional prion-like protein, the translation regulator Orb2 to be sequestered by Htt aggregates. Coexpression of Orb2 can partially rescue the lethality associated with poly Q expanded Htt. These findings can be relevant for HD as human homologs of Orb2 also can be sequestered by pathogenic Htt aggregates. Our work suggests that translation dysfunction could be one of the contributors in the pathogenesis of HD and new therapies targeting protein synthesis pathways might help alleviate disease symptoms.

cell biology↗