Abstract
Objectives
The purpose of this study was to investigate the expression of T-cell immunoglobulin and ITIM domain (TIGIT) in peripheral circulation of primary Sjögren’s syndrome (pSS) and its role in the development of pSS.
Methods
The expression of TIGIT on T cells, B cells, natural killer (NK) cells, and CD14 + monocytes was detected by flow cytometry in pSS and healthy control (HC). The correlations between expression of TIGIT and clinical features and laboratory parameters of pSS were analyzed. Meanwhile, we analyzed the change in expression of TIGIT before and after treatment, and its role in the prognosis of pSS treatment was evaluated.
Results
The expression of TIGIT on CD3 + , CD4 + , and CD8 + T cells increased and decreased on CD14 + monocytes in pSS compared to HC; however, there was no significance of B lymphocytes and NK cells. The correlation analysis between the expression of TIGIT on T lymphocytes and CD14 + monocytes and clinical features of pSS showed that the decrease in TIGIT expression on CD14 + monocytes was more closely related to pSS. The expression of TIGIT + CD14 + monocytes negatively correlated with the disease activity of pSS. The expression of TIGIT + CD14 + monocytes of pSS with arthralgia, fatigue, decayed tooth, xerostomia, interstitial lung disease, anti-Ro52 positive, and high IgG decreased compared to that in negative patients. Furthermore, it was significantly lower in active patients than in nonactive patients. After treatment, the expression of TIGIT + CD14 + monocytes tended to increase.
Conclusion
Our study suggested that decreased TIGIT expression on CD14 + monocytes was associated with the clinical manifestations, disease activity, and prognosis of pSS patients. TIGIT + CD14 + monocytes may present as a potential target and a biomarker of the prognosis for immunomodulatory therapy in pSS.
Key Points • The expression of TIGIT+CD14+ monocytes significantly decreased in pSS patients compared to HC. • There was a negative correlation between TIGIT+CD14+ monocytes and the disease activity of pSS. • TIGIT+CD14+ monocyte expression was associated with the clinical manifestations, autoantibodies, IgG, and prognosis of pSS patients. |
Similar content being viewed by others
Data availability
The data sets generated during and/or analyzed during the current study are available from the corresponding authors on reasonable request.
References
Negrini S, Emmi G, Greco M (2022) Sjögren’s syndrome: a systemic autoimmune disease. Clin Exp Med 22:9–25
Verstappen GM, Kroese F, Bootsma H (2019) T cells in primary Sjogren’s syndrome: targets for early intervention. Rheumatology (Oxford). https://doi.org/10.1093/rheumatology/kez004
Deng C, Chen Y, Li W et al (2020) Alteration of CD226/TIGIT immune checkpoint on T cells in the pathogenesis of primary Sjogren’s syndrome. J Autoimmun 113:102485. https://doi.org/10.1016/j.jaut.2020.102485
Yasutomi M, Christiaansen AF, Imai N et al (2022) CD226 and TIGIT cooperate in the differentiation and maturation of human Tfh cells. Front Immunol 13:840457. https://doi.org/10.3389/fimmu.2022.840457
Yue C, Gao S, Li S et al (2022) TIGIT as a promising therapeutic target in autoimmune diseases. Front Immunol 13:911919. https://doi.org/10.3389/fimmu.2022.911919
Nandi SS, Gohil T, Sawant SA et al (2022) CD155: a key receptor playing diversified roles. Curr Mol Med 22:594–607. https://doi.org/10.2174/1566524021666210910112906
Preillon J, Cuende J, Rabolli V et al (2021) Restoration of T-cell effector function, depletion of Tregs, and direct killing of tumor cells: the multiple mechanisms of action of a-TIGIT antagonist antibodies. Mol Cancer Ther 20:121–131. https://doi.org/10.1158/1535-7163.MCT-20-0464
Yu Y, Chen Z, Wang Y et al (2021) Infliximab modifies regulatory T cells and co-inhibitory receptor expression on circulating T cells in psoriasis. Int Immunopharmacol 96:107722. https://doi.org/10.1016/j.intimp.2021.107722
Battella S, Oliva S, Franchitti L (2019) Finetuning of the DNAM-1TIGIT ligand axis in mucosal t cells and its dysregulation in pediatric inflflammatory bowel diseases (IBD). Mucosal Immunol 2019(12):1358–69
Yang M, Liu Y, Mo B et al (2019) Helios but not CD226, TIGIT and Foxp3 is a potential marker for CD4+Treg cells in patients with rheumatoid arthritis. Cell Physiol Biochem 52(5):1178–9252. https://doi.org/10.33594/000000080
Lucca LE, Axisa PP, Singer ER et al (2019) TIGIT signaling restores suppressor function of Th1 Tregs. JCI Insight 4(3). https://doi.org/10.1172/jci.insight.124427
Wang FF, Wang Y, Wang L et al (2018) TIGIT expression levels on CD4+ T cells are correlated with disease severity in patients with psoriasis. Clin Exp Dermatol 43:675–682. https://doi.org/10.1111/ced.13414
Luo Q, Li X, Fu B et al (2018) Decreased expression of TIGIT in NK cells correlates negatively with disease activity in systemic lupus erythematosus. Int J Clin Exp Pathol 11(5):2408–2418
Seror R, Ravaud P, Bowman SJ et al (2010) EULAR Sjögren’s syndrome disease activity index: development of a consensus systemic disease activity index for primary Sjögren’s syndrome. Ann Rheum Dis 69:1103–1109. https://doi.org/10.1136/ard.2009.110619
Seror R, Theander E, Brun JG et al (2015) Validation of EULAR primary Sjogren’s syndrome disease activity (ESSDAI) and patient indexes (ESSPRI). Ann Rheum Dis 74:859–866. https://doi.org/10.1136/annrheumdis-2013-204615
Sarrand J, Baglione L, Parisis D et al (2022) The involvement of alarmins in the pathogenesis of Sjögren’s syndrome. Int J Mol Sci 23:5671. https://doi.org/10.3390/ijms23105671
Zhou H, Li B, Li J et al (2019) Dysregulated T cell activation and aberrant cytokine expression profile in systemic lupus erythematosus. Mediators Inflamm 2019:8450911–8450947. https://doi.org/10.1155/2019/8450947
Dean JW, Peters LD, Fuhrman CA et al (2020) Innate inflammation drives NK cell activation to impair Treg activity. J Autoimmun 108:102417. https://doi.org/10.1016/j.jaut.2020.102417
Felix KM, Teng F, Bates NA et al (2019) P2RX7 deletion in T cells promotes autoimmune arthritis by unleashing the Tfh cell response. Front Immunol 10:411. https://doi.org/10.3389/fimmu.2019.00411
Muhammad F, Wang D, McDonald T et al (2020) TIGIT(+) A2Ar-Dependent anti-uveitic Treg cells are a novel subset of Tregs associated with resolution of autoimmune uveitis. J Autoimmun 111:102441. https://doi.org/10.1016/j.jaut.2020.102441
Liu S, Sun L, Wang C et al (2019) Treatment of murine lupus with TIGIT-Ig. Clin Immunol 203:72–80. https://doi.org/10.1016/j.clim.2019.04.007
Luo Q, Deng Z, Xu C et al (2017) Elevated expression of immunoreceptor tyrosine-based inhibitory motif (TIGIT) on T lymphocytes is correlated with disease activity in rheumatoid arthritis. Med Sci Monit 23:1232–41. https://doi.org/10.12659/MSM.902454
Luo Q, Ye J, Zeng L et al (2017) Elevated expression of TIGIT on CD3 + CD4 + T cells correlates with disease activity in systemic lupus erythematosus. Allergy Asthma Clin Immunol 13:15. https://doi.org/10.1186/s13223-017-0188-7
Wang F, Hou H, Wu S et al (2015) TIGIT expression levels on human NK cells correlate with functional heterogeneity among healthy individuals. Eur J Immunol 45:2886–2897. https://doi.org/10.1002/eji.201545480
Zhao J, Li L, Yin H et al (2023) TIGIT: an emerging immune checkpoint target for immunotherapy in autoimmune disease and cancer. Int Immunopharmacol 120:110358. https://doi.org/10.1016/j.intimp.2023.110358
Lozano E, Dominguez-Villar M, Kuchroo V et al (2012) The TIGIT/CD226 axis regulates human T cell function. J Immunol 188:3869–3875. https://doi.org/10.4049/jimmunol.1103627
Zhao W, Dong Y, Wu C et al (2016) TIGIT overexpression diminishes the function of CD4 T cells and ameliorates the severity of rheumatoid arthritis in mouse models. Exp Cell Res 340:132–138. https://doi.org/10.1016/j.yexcr.2015.12.002
Negrini S, Emmi G, Greco M et al (2022) Sjögren’s syndrome: a systemic autoimmune disease. Clin Exp Med 22:9–25. https://doi.org/10.1007/s10238-021-00728-6
Mao L, Hou H, Wu S et al (2017) TIGIT signalling pathway negatively regulates CD4(+) T-cell responses in systemic lupus erythematosus. Immunology 151:280–290. https://doi.org/10.1111/imm.12715
Stefanski AL, Tomiak C, Pleyer U et al (2017) The Diagnosis and Treatment of Sjögren ’ s Syndrome. Dtsch Arztebl Int 114:354–361
Jantz-Naeem N, Böttcher-Loschinski R, Borucki K, et al. (2023) TIGIT signaling and its influence on T cell metabolism and immune cell function in the tumor microenvironment. Front Oncol 13:1060112. https://doi.org/10.3389/fonc.2023.1060112
Yoshimoto K, Suzuki K, Takei E et al (2020) Elevated expression of BAFF receptor, BR3, on monocytes correlates with B cell activation and clinical features of patients with primary Sjogren’s syndrome. Arthritis Res Ther 22:157. https://doi.org/10.1186/s13075-020-02249-1
Jariwala N, Benoit B, Kossenkov AV et al (2017) TIGIT and Helios are highly expressed on CD4+ T cells in Sézary syndrome patients. J Invest Dermatol 137:257–260. https://doi.org/10.1016/j.jid.2016.08.016
Joller N, Lozano E, Burkett PR et al (2014) Treg cells expressing the coinhibitory molecule TIGIT selectively inhibit proinflammatory Th1 and Th17 cell responses. Immunity (Cambridge, Mass) 40:569–81. https://doi.org/10.1016/j.immuni.2014.02.012
Acknowledgements
We sincerely thank the platform provided by the Jiangsu Institute of Clinical Immunology and Jiangsu Key Laboratory of Clinical Immunology. We are grateful for the help provided by all departments of rheumatology in the First Affiliated Hospital of Soochow University.
Funding
The study was funded by the Science and Technology Programme of Suzhou (SLJ2021009), the Natural Science Key Project of Bengbu Medical College (2022byzd070), the National Natural Science Foundation of China (81873876), and the Gusu Talent Project of Suzhou (nos. GSWS2020011 and GSWS2020018).
Author information
Authors and Affiliations
Contributions
P.Z., CP.L., and X.C. designed the study, conducted the experiment, performed the data analysis, and wrote the manuscript. C.P., W.C., and XY.F. participated in the sample and clinical data collection. YH.Y. and C.S. participated in patient enrollment and disease activity evaluation. Y.S. assisted the experiment of this study. J.W. and CP.L helped optimize the research, proofread the paper, and revised the manuscript. All authors helped with the final approval of the version.
Corresponding authors
Ethics declarations
Disclosures
None.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Jian Wu is the first corresponding author, and Cuiping Liu is the co-corresponding author.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Zhao, P., Peng, C., Chang, X. et al. Decreased expression of TIGIT on CD14 + monocytes correlates with clinical features and laboratory parameters of patients with primary Sjögren’s syndrome. Clin Rheumatol 43, 297–306 (2024). https://doi.org/10.1007/s10067-023-06759-6
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10067-023-06759-6