Sjögren’s disease predominantly affects the salivary and lacrimal glands, resulting in tissue inflammation characterized by the formation of tertiary lymphoid structures and subsequent loss of glandular function. This leads to symptoms such as dryness of the eyes and mouth, fatigue, and diminished health-related quality of life. Salivary gland epithelial cells play a crucial pathogenic role in this disease.
Saba Nayar, author of the study, emphasized the need for a comprehensive understanding of the salivary gland microenvironment to effectively treat patients. However, current profiling efforts often struggle to capture high-plex 'omics data while preserving tissue spatial architecture. To address this challenge, researchers meticulously mapped cell types and novel populations, identifying eight distinct neighborhoods within the tissue. Some neighborhoods were enriched with epithelial cells, while others correlated with various immune cell populations.
Notably, one neighborhood stood out for its enrichment of IgA plasma cells, associated with myeloid populations, in contrast to other IgG plasma cell niches. This groundbreaking spatial mapping work, presented during a basic abstract session on new pathways in Sjögren’s disease, holds promise for revealing novel cellular landscapes and their interactions, ultimately aiding therapeutic discoveries.
The second abstract focused on salivary gland epithelial cells (SGEC), which are known to contribute to Sjögren’s disease pathogenesis. Researchers are actively developing and characterizing differentiated organoids derived from minor salivary gland biopsies of both patients and sicca controls. These organoids exhibit comparable self-renewal capacity for long-term culture and express epithelial ductal and acinar markers, recapitulating epithelial diversity. Notably, exposure to pilocarpine induced increased calcium levels in the organoids, suggesting their capacity to secrete saliva in response to cholinergic stimulation. However, this effect was diminished in organoids derived from Sjögren’s patients compared to controls.
Author of the study, Loïc Meudec, highlighted ongoing investigations aimed at developing immuno-organoids. These specialized models will facilitate the study of crosstalk between epithelial cells and immune cells, as well as the testing of drug effects on this intricate interplay.