Spatial transcriptomic profiling identifies lacrimal gland epithelial cell-driven mechanisms underlying autoimmunity in Sjögren's disease.
| Title: | Spatial transcriptomic profiling identifies lacrimal gland epithelial cell-driven mechanisms underlying autoimmunity in Sjögren's disease. |
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| Authors: | Gupta S; Department of Ophthalmology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA.; Athanasios Ploumakis; The Spatial Technologies Unit, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.; Kalavros N; The Spatial Technologies Unit, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.; Masli S; Department of Ophthalmology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA. |
| Source: | BioRxiv : the preprint server for biology [bioRxiv] 2025 Nov 05. Date of Electronic Publication: 2025 Nov 05. |
| Publication Type: | Journal Article; Preprint |
| Language: | English |
| Journal Info: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| Abstract: | Sjögren's disease (SjD) is a second most prevalent rheumatic disease involving autoimmune pathology of tear-producing lacrimal glands that leads to a common clinical manifestation of chronic ocular surface disease. Despite advances in understanding of SjD, lacrimal gland pathology remains incompletely understood limiting diagnosis and treatment. Here we analyze spatial transcriptomic profile of lacrimal glands from wild-type (C57Bl/6) mice and Thrombospondin (TSP)-1-/- mice, a spontaneous mouse model of SjD. We uncover molecular mechanisms underlying functional loss of major epithelial cell subtypes - acinar, duct and myoepithelial cells. We identify potential early mechanisms and markers of glandular damage. By integrating spatial and cellular profiles, we uncover the presence of antigen presenting cells in the proximity of duct epithelial cells that were not described previously in lacrimal glands. We further identify role of epithelial cells as active participants in promoting or sustaining inflammation. Our findings help reveal potential molecular and cellular cues that drive periductal infiltrates containing B cells and Tfh cells that form germinal centers to facilitate local autoantibody production. Overall, our study can provide a framework for therapeutic targeting of epithelial cell types and multicellular interactions underlying autoimmune pathology. |
| Comments: | Update in: Front Immunol. 2026 Mar 05;17:1759347. doi: 10.3389/fimmu.2026.1759347.. (PMID: 41869322) |
| Grant Information: | R56 EY035213 United States EY NEI NIH HHS |
| Contributed Indexing: | Keywords: Autoimmunity; Biological Sciences (Major); Lacrimal gland; Medical Sciences (Minor); Ophthalmology; Sjögren’s disease; Spatial transcriptomics |
| Entry Date(s): | Date Created: 20251124 Date Completed: 20260325 Latest Revision: 20260325 |
| Update Code: | 20260326 |
| PubMed Central ID: | PMC12637439 |
| DOI: | 10.1101/2025.11.03.686353 |
| PMID: | 41278932 |
| Database: | MEDLINE |
Journal Article; Preprint