Tissue-Specific Expansion of Age-Associated B Cells via IFN-γ and IL-21 Within Salivary Glands in Sjögren Disease - PubMed
3 hours ago
- #Autoimmunity
- #Age-associated B cells
- #Sjögren disease
- Sjögren disease (SjD) is an autoimmune disorder affecting exocrine glands, with age as a significant risk factor.
- Age-associated B cells (ABCs) increase with age and are implicated in autoimmune responses, particularly in SjD.
- Study examined labial salivary glands (LSGs) from 44 SjD patients and 11 non-SjD controls, finding T-bet+ CD20+ ABCs infiltrating SjD patients' glands, especially in those aged 40s-60s.
- In a SjD mouse model, ABCs (CD11b+ CD95+ CD19+) accumulated locally in salivary glands (SGs) earlier than in controls, remaining low in cervical lymph nodes (cLNs).
- IL-21 and IFN-γ were identified as key factors in ABC differentiation, with IL-21 from CD4+ T cells and autocrine IFN-γ from ABCs promoting their expansion.
- CD4+ T cells, particularly follicular helper T (Tfh)-like cells, were a major source of IL-21 in SGs of mature-adult SjD mice.
- ABCs showed elevated IFN-γ expression compared to other immune cells, suggesting an autocrine mechanism driving their expansion.
- Findings suggest localized ABC expansion in SGs contributes to autoimmune tissue damage in SjD, offering potential therapeutic targets.
- Study provides insights into how aging-associated immune changes may drive SjD development and progression.