Details

Autor(en) / Beteiligte

• Joachims, Michelle L
• Leehan, Kerry M
• Dozmorov, Mikhail G
• Georgescu, Constantin
• Pan, Zijian
• Lawrence, Christina
• Marlin, M Caleb
• Macwana, Susan
• Rasmussen, Astrid
• Radfar, Lida
• Lewis, David M
• Stone, Donald U
• Grundahl, Kiely
• Scofield, R Hal
• Lessard, Christopher J
• Wren, Jonathan D
• Thompson, Linda F
• Guthridge, Joel M
• Sivils, Kathy L
• Moore, Jacen S
• Farris, A Darise

Titel

Sjögren's Syndrome Minor Salivary Gland CD4 + Memory T Cells Associate with Glandular Disease Features and have a Germinal Center T Follicular Helper Transcriptional Profile

Ist Teil von

• Journal of clinical medicine, 2020-07, Vol.9 (7), p.2164

Ort / Verlag

Switzerland: MDPI AG

Erscheinungsjahr

2020

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• To assess the types of salivary gland (SG) T cells contributing to Sjögren's syndrome (SS), we evaluated SG T cell subtypes for association with disease features and compared the SG CD4 memory T cell transcriptomes of subjects with either primary SS (pSS) or non-SS sicca (nSS). SG biopsies were evaluated for proportions and absolute numbers of CD4 and CD8 T cells. SG memory CD4 T cells were evaluated for gene expression by microarray. Differentially-expressed genes were identified, and gene set enrichment and pathways analyses were performed. CD4 CD45RA T cells were increased in pSS compared to nSS subjects (33.2% vs. 22.2%, < 0.0001), while CD8 CD45RA T cells were decreased (38.5% vs. 46.0%, = 0.0014). SG fibrosis positively correlated with numbers of memory T cells. Proportions of SG CD4 CD45RA T cells correlated with focus score (r = 0.43, < 0.0001), corneal damage (r = 0.43, < 0.0001), and serum Ro antibodies (r = 0.40, < 0.0001). Differentially-expressed genes in CD4 CD45RA cells indicated a T follicular helper (Tfh) profile, increased homing and increased cellular interactions. Predicted upstream drivers of the Tfh signature included TCR, TNF, TGF-β1, IL-4, and IL-21. In conclusion, the proportions and numbers of SG memory CD4 T cells associate with key SS features, consistent with a central role in disease pathogenesis.