Project description:Background: Atopic dermatitis (AD) predominantly affects young children, but our understanding of AD pathogenesis is based on skin and blood samples from longstanding adult AD. Genomic biopsy profiling from early pediatric AD showed significant Th2 and Th17/Th22-skewing, without the characteristic adult Th1 up-regulation. Since obtaining pediatric biopsies is difficult, blood gene expression profiling may provide a surrogate for the pediatric skin signature. Objective: To define the blood profile and associated biomarkers of early moderate-to-severe pediatric AD. Methods: We compared microarrays and RT-PCR of blood cells from 28 AD children (<5yrs and within 6 months of disease onset) to healthy control blood cells. Differentially expressed genes/DEGs in blood (fold change/FCH>1.2 and false discovery rate/FDR<0.05) were then compared with skin DEGs. Results: Eosinophil and Th2 markers (IL5RA, IL1RL1/ST2, HRH4, CCR3, SIGLEC8, PRSS33, CLC from gene arrays; IL13/IL4/CCL22 from RT-PCR) were upregulated in early pediatric AD blood, while IFNG/Th1 was decreased. Th1 markers were negatively correlated with clinical severity (EASI, pruritus, transepidermal water loss/TEWL), whereas Th2/Th17-induced IL19 was positively correlated with SCORAD. While a few RT-PCR-defined immune markers (IL13/CCL22) were increased in blood, as previously also reported for skin, there was minimal overlap based on gene array DEGs. Conclusion: The whole blood signature of early moderate-to-severe pediatric AD blood cells show predominantly a Th2/eosinophil profile, but markers largely differ from the skin profile. Given their complementarity, pooling of biomarkers from blood and skin may improve profiling and predictions, providing insight regarding disease course allergic comorbidity development, and response to systemic medications.
Project description:Aging is a multifaceted systemic process that contributes to the onset of age-related diseases. Despite advances, few comprehensive anti-aging strategies have successfully reversed the adverse effects of aging. Heterochronic parabiosis studies have highlighted the potential of systemic rejuvenation through blood-borne factors, yet the precise drivers of aging and rejuvenation, along with their mechanisms, remain largely elusive. Furthermore, translating these findings to humans has been challenging. In this study, we achieved human skin rejuvenation through systemic factors using a microphysiological system comprising a 3D skin model and a 3D bone marrow model, which simulates the niche for progenitor and blood cells. Treatment with young human serum, compared to aged human serum, enhanced cell proliferation and reduced the biological age of skin tissue, as determined by methylation-based age clocks. Notably, these effects required the presence of bone marrow-derived cells in the system. Further analysis of the bone marrow model revealed serum-dependent changes in cell population composition and aging markers. Proteome profiling identified 55 potential systemic rejuvenating proteins secreted by bone marrow-derived cells. Among these, seven proteins were validated to have rejuvenating effects on human skin cells through hallmark aging assays, underscoring their role as key systemic factors in reversing skin aging.
Project description:Hidradenitis suppurativa (HS) is an inflammatory skin disease with limited therapeutic options. We and others have previously identified an abnormal B cell infiltrate within HS lesional skin. We performed scRNASequencing on CD3 negative cells from inflammatory HS skin lesions, healthy control skin and matched blood to better understand infiltrating B cells amongst other immune cells within lesional skin.
Project description:The main objective of our study was to determine whether central biologic processes inferred from transcriptomic profiling of distal airspace mononuclear cells are reflected among circulating peripheral blood mononuclear cells (PBMCs) during the acute phase of ARDS. To compare mononuclear cells from the airspaces and bloodstream we collected paired peripheral blood and non-bronchoscopic BAL (NBBAL) samples from mechanically ventilated patients with severe ARDS and enriched for mononuclear cells using density centrifugation and cryopreservation. We then performed bulk RNA sequencing and evaluated gene expression profiles and gene expression networks between compartments.
