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Article

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

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Oklahoma Medical Research Foundation, Arthritis & Clinical Immunology Program, 825 NE 13th Street, Oklahoma City, OK 73104, USA
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College of Dentistry, University of Oklahoma Health Sciences Center, 1201 N Stonewall Avenue, Oklahoma City, OK 73117, USA
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Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, 608 Stanton L. Young Boulevard, Oklahoma City, OK 73104, USA
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Department of Medicine, University of Oklahoma Health Sciences Center, 1100 N Lindsay Avenue, Oklahoma City, OK 73104, USA
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Department of Veteran’s Affairs Medical Center, 931 NE 13th Street, Oklahoma City, OK 73104, USA
*
Author to whom correspondence should be addressed.
Current Affiliation: Department of Pathology, Department of Biostatistics, Virginia Commonwealth University, 830 E. Main St., Richmond, VA 23298, USA.
Current Affiliation: Oklahoma Medical Research Foundation, Genes and Human Disease Research Program, 825 NE 13th Street, Oklahoma City, OK 73104, USA.
§
Current Affiliation: Spokane Eye Clinic, 427 S Bernard Street, Spokane, WA 99204, USA.
Current Affiliation: Department of Diagnostic and Health Sciences, Clinical Laboratory Science Program, University of Tennessee Health Science Center, 910 Madison Avenue, Memphis, TN 38163, USA.
J. Clin. Med. 2020, 9(7), 2164; https://doi.org/10.3390/jcm9072164
Received: 3 June 2020 / Revised: 25 June 2020 / Accepted: 6 July 2020 / Published: 8 July 2020
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%, p < 0.0001), while CD8+CD45RA T cells were decreased (38.5% vs. 46.0%, p = 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, p < 0.0001), corneal damage (r = 0.43, p < 0.0001), and serum Ro antibodies (r = 0.40, p < 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. View Full-Text
Keywords: sjögren’s syndrome; salivary gland; T lymphocytes; transcriptome sjögren’s syndrome; salivary gland; T lymphocytes; transcriptome
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MDPI and ACS Style

Joachims, M.L.; Leehan, K.M.; Dozmorov, M.G.; Georgescu, C.; Pan, Z.; Lawrence, C.; Marlin, M.C.; Macwana, S.; Rasmussen, A.; Radfar, L.; Lewis, D.M.; Stone, D.U.; Grundahl, K.; Scofield, R.H.; Lessard, C.J.; Wren, J.D.; Thompson, L.F.; Guthridge, J.M.; Sivils, K.L.; Moore, J.S.; Farris, A.D. 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. J. Clin. Med. 2020, 9, 2164. https://doi.org/10.3390/jcm9072164

AMA Style

Joachims ML, Leehan KM, Dozmorov MG, Georgescu C, Pan Z, Lawrence C, Marlin MC, Macwana S, Rasmussen A, Radfar L, Lewis DM, Stone DU, Grundahl K, Scofield RH, Lessard CJ, Wren JD, Thompson LF, Guthridge JM, Sivils KL, Moore JS, Farris AD. 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. Journal of Clinical Medicine. 2020; 9(7):2164. https://doi.org/10.3390/jcm9072164

Chicago/Turabian Style

Joachims, Michelle L., Kerry M. Leehan, Mikhail G. Dozmorov, Constantin Georgescu, Zijian Pan, Christina Lawrence, M. C. Marlin, Susan Macwana, Astrid Rasmussen, Lida Radfar, David M. Lewis, Donald U. Stone, Kiely Grundahl, R. H. Scofield, Christopher J. Lessard, Jonathan D. Wren, Linda F. Thompson, Joel M. Guthridge, Kathy L. Sivils, Jacen S. Moore, and A. D. Farris 2020. "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" Journal of Clinical Medicine 9, no. 7: 2164. https://doi.org/10.3390/jcm9072164

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