The interplay among different cells in a tissue is essential for maintaining homeostasis. Although disease states have been traditionally attributed to individual cell types, increasing evidence and new therapeutic options have demonstrated the primary role of multicellular functions to understand health and disease, opening new avenues to understand pathogenesis and develop new treatment strategies. We recently described the cellular composition and dynamics of the human oral mucosa; however, the spatial arrangement of cells is needed to better understand a morphologically complex tissue. Here, we link single-cell RNA sequencing, spatial transcriptomics, and high-resolution multiplex fluorescence in situ hybridisation to characterise human oral mucosa in health and oral chronic inflammatory disease. We deconvolved expression for resolution enhancement of spatial transcriptomic data and defined highly specialised epithelial and stromal compartments describing location-specific immune programs. Furthermore, we spatially mapped a rare pathogenic fibroblast population localised in a highly immunogenic region, responsible for lymphocyte recruitment through CXCL8 and CXCL10 and with a possible role in pathological angiogenesis through ALOX5AP. Collectively, our study provides a comprehensive reference for the study of oral chronic disease pathogenesis.
BACKGROUND/AIMS: Protocol biopsies offer new possibilities to predict kidney allograft outcome. The aim of this study was to find clinical, laboratory, morphological and molecular predictors of short-term renal graft survival. METHODS: Three-month protocol kidney graft biopsy was carried out on 257 patients. The real-time RT-PCR was used to identify intragraft mRNA expression of several cytokines and chemokines and predictive statistics was performed to find markers connected with the risk of premature graft failure. RESULTS: Compared to patients with normal morphology at 3 months, patients with subclinical rejection including borderline changes had experienced more frequent (p < 0.001) acute rejections before 3-month biopsy, serum creatinine >or=170 micromol/l (p < 0.01), and higher intrarenal expression of RANTES, IP-10 (p < 0.001), C3, CD3, IgJ (p < 0.01) and CD20 (p < 0.05). There was a significant correlation between subclinical rejection and the occurrence of late acute rejection and graft failure at the first year after transplantation. Moreover, higher RANTES and IP-10 expressions in subclinical rejection predicted graft loss at one year after transplantation in the univariate analysis. CONCLUSIONS: Patients with subclinical rejection including borderline changes in 3-month biopsy and particularly those with higher intrarenal expression of RANTES and IP-10 mRNA were found to be at risk for premature kidney graft loss.
- MeSH
- antigeny CD20 genetika MeSH
- antigeny CD3 genetika MeSH
- biologické markery MeSH
- biopsie MeSH
- chemokin CCL5 genetika MeSH
- chemokin CXCL10 genetika MeSH
- dospělí MeSH
- imunosupresiva terapeutické užití MeSH
- komplement C3 genetika MeSH
- kreatinin krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- messenger RNA metabolismus MeSH
- následné studie MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- prediktivní hodnota testů MeSH
- rejekce štěpu diagnóza farmakoterapie epidemiologie imunologie MeSH
- rizikové faktory MeSH
- testování histokompatibility MeSH
- transplantace ledvin MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
