Upregulation of GPR65 in pathogenic Th17 Cells and inflammatory regions in ankylosing spondylitis: insights from scRNA-seq and histological analysis 2600
Year: 2025
Type: article
Study design: Observational Study
Abstract: Description Background/Purpose: Ankylosing spondylitis (AS) is a chronic inflammatory spine disease driven by pathogenic Th17 (pTh17) cells. Identifying and therapeutic targets for pTh17 cells could lead to new treatments. Recent scRNA-seq studies found GPR65 highly upregulated in pTh17 cells, suggesting its potential as a therapeutic target. Methods Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) from AS patients were isolated for single-cell RNA sequencing (scRNA-seq) and CITE-seq to profile T cell subsets. Spinal tissue samples from AS patients and healthy controls (HCs) were examined with immunohistochemistry to assess GPR65 expression. Immunofluorescence staining for GPR65, CD4, and IL-17 was performed on spinal tissues to confirm GPR65’s presence in Th17 cells. Results CITE-seq analysis revealed distinct T cell subsets with GPR65 significantly upregulated in the pTh17 cluster, marking its pathogenic potential. Immunohistochemistry indicated higher GPR65 expression in AS spinal tissues than in HCs, especially in inflammation-prone regions. Immunofluorescence confirmed GPR65 co-localization with IL-17-producing CD4+ T cells, linking it to AS-related inflammation. Conclusion The findings demonstrate that GPR65 is highly expressed in pTh17 cells and inflammatory spinal regions in AS, particularly in IL-17-producing CD4+ T cells, supporting its role as a promising therapeutic target for managing AS progression. Topic Categories Immune Mechanisms of Human Disease (HUM)
Source: The Journal of Immunology
Authors: Tae-Jong Kim, Sungsin Joo, Jeong Seok Lee, Eun Young Lee, Tae-Hwan Kim
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4416446424
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