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Olmedo, V.

Publications and source records attributed to Olmedo, V..

3 recordsLinked to original sources

Clonally Convergent Tph/Tfh-like CD4+ T Cells are Shared Across Recovery and Recurrence in Experimental Periodontitis

Periodontitis is a chronic inflammatory disease of the tooth-supporting structures (periodontium) that requires life-long maintenance to prevent progression. Using a sensitized model of recurrent periodontitis in mice (SeRPD), in which regulatory breakdown was induced by temporary Treg depletion concurrent with disease, we mapped the gingival T cell imprint across each disease phase. Transient regulatory breakdown left a durable mucosal imprint after clinical recovery, characterized by enrichment of local and regional CD4 T cells. Paired single-cell RNA and TCR sequencing of gingival immune cells identified a convergent clonotype expanded from recovery into recurrence that carried a Tfh/Tph-like transcriptional identity. An analogous CD4 T cell population was detected in human periodontitis lesions by single-cell transcriptomics. Together, these findings support a paradigm in which clinical recovery does not ensure a local T cell repertoire reset; instead, a reservoir of antigen-experienced, tissue-adapted CD4 T cells persist in the mucosa and participate in recurrence.

immunology↗

A decrease in specific health-associated commensals is linked to progressive periodontal tissue destruction independent of dysbiotic community profiles

Periodontitis is a chronic inflammatory disease associated with dysbiotic microbial communities that leads to destruction of the tooth-supporting tissues. The transition from host-microbial periodontal homeostasis to disease remains poorly understood. The murine ligature-induced periodontitis model was employed to characterize the temporal dynamics of the subgingival microbiome and host tissue features. Ligatures were placed in C57BL/6N mice, and collected on days 0, 1, 3, 5, and 7 post-induction. Bacterial load, alveolar bone loss, immune cells (CD45), cells with osteoclastogenic potential (TRAP) and collagen destruction were analyzed. Additionally, the V4 region of the 16S rRNA gene was sequenced for ecological analyses, including co-occurrence networks and functional prediction. Spatial distribution of the most abundant species was visualized using CLASI-FISH microscopy. Finally, association models were performed to link bacterial abundances with time and tissue parameters. The most substantial microbial shift occurred on day 1, and a dysbiotic community was established by day 3. CD45 cell infiltration increased as early as day 1, preceding the rise in TRAP cells on day 3 and the onset of tissue destruction on day 5. By day 7, predicted bacterial functions included protein export, lipid and galactose metabolism. Health-associated taxa were identified, and their abundance correlated positively with collagen integrity and negatively with immune cell infiltration and bacterial load, highlighting their role in homeostasis. These findings provide a high-resolution temporal map of microbiome-host interactions during experimental periodontitis establishment and identify specific microbial and cellular windows for potential therapeutic intervention.

microbiology↗

Agreement between 18F-Florbetapir PET imaging and cerebrospinal fluid Aβ1-42, Aβ1-40, tTau and pTau measured on the LUMIPULSE G fully automated platform

INTRODUCTIONThe development of fully automated immunoassay platforms has improved the technical reliability of cerebrospinal fluid (CSF) biomarkers for Alzheimers disease.\n\nMETHODSWe quantified A{beta}1-42, A{beta}1-40, tTau and pTau levels using the Lumipulse G System in 94 CSF samples from participants of the SPIN cohort with available 18F-Florbetapir imaging. Amyloid scans were assessed visually and through automated quantification. We determined the cutoffs of CSF biomarkers that optimized their agreement with 18F-Florbetapir PET and evaluated concordance between markers of the amyloid category.\n\nRESULTSA{beta}1-42, tTau and pTau (but not A{beta}1-40) and the ratios with A{beta}1-42 had good diagnostic agreement with 18F-Florbetapir PET. As a marker of amyloid pathology, the A{beta}1-42/A{beta}1-40 ratio had higher agreement and better correlation with amyloid PET than A{beta}1-42 alone.\n\nDISCUSSIONCSF biomarkers measured with the Lumipulse G System show good agreement with amyloid imaging. Combination of A{beta}1-42 with A{beta}1-40 increases the agreement between markers of amyloid pathology.

neuroscience↗