ArticleArthritis research & therapy2021
Expansion of circulating peripheral TIGIT+CD226+ CD4 T cells with enhanced effector functions in dermatomyositis.
Article in Arthritis research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 22 citations in OpenAlex.
- Review
- An update on the pathogenesis of idiopathic inflammatory myopathies.Current opinion in rheumatology · 2025Review
- CD226Frontiers in immunology · 2025Article
- Anti-MDA5 antibody-positive dermatomyositis: pathogenesis and clinical progress.Nature reviews. Rheumatology · 2024Review
- Dysregulated CD38 expression on T cells was associated with rapidly progressive interstitial lung disease in anti-melanoma differentiation-associated gene 5 positive dermatomyositis.Frontiers in immunology · 2024Article
- Upregulation of the CD155-CD226 Axis Is Associated With Muscle Inflammation and Disease Severity in Idiopathic Inflammatory Myopathies.Neurology(R) neuroimmunology & neuroinflammation · 2023Article
- Imbalance of peripheral blood Th17/Treg increases neutrophil-to-lymphocyte ratio in patients with dermatomyositis.American journal of translational research · 2023Article
- Increased TIGITExperimental and therapeutic medicine · 2022Article
- The CD226/TIGIT axis is involved in T cell hypo-responsiveness appearance in long-term kidney transplant recipients.Scientific reports · 2022Article
- Role of the tumor immune microenvironment in tumor immunotherapy.Oncology letters · 2022Review
- TIGIT as a Promising Therapeutic Target in Autoimmune Diseases.Frontiers in immunology · 2022Review
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundT cell Ig and ITIM domain (TIGIT)/CD226 pathway has a critical role in regulating T cell responses and has come to the forefront in cancer as a promising immunotherapeutic target. However, its role in autoimmune diseases is just beginning to be elucidated. Dermatomyositis (DM) is an autoimmune disease, in which T cell dysregulation plays a pivotal role, and importantly, it is a common immune-related adverse event in response to treatment of cancers with immune checkpoint inhibitors, but no studies have implicated the TIGIT/CD226 axis in DM.
methodsWe recruited 30 treatment-naïve DM patients and 26 healthy controls. Flow cytometry analysis was used to investigate the co-expression of TIGIT and CD226 on T cells in blood samples. Magnetic bead or FACS-based cell isolation, T cell proliferation assay, and intracellular cytokine staining were performed to analyze the functions of different TIGIT/CD226 phenotypes. Recombinant proteins CD155, CD112, and anti-CD226 antibodies were used to suppress the function of TIGIT/CD226-expressing CD4 T cells.
resultsFour distinct subsets of T cells based on TIGIT/CD226 co-expression, TIGIT+CD226-, TIGIT+CD226+, TIGIT-CD226+, and TIGIT-CD226-, were identified and characterized in DM patients. Our data showed that the function of CD4 T cell subset varied by the TIGIT/CD226 phenotype. An elevated TIGIT+CD226+ CD4 subset with enhanced effector function was observed in patients with DM, especially the patients complicated with interstitial lung disease. This subpopulation was closely related to DM activity and decreased significantly in DM remission after treatment. Furthermore, the effector function of TIGIT+CD226+ CD4 subset could be suppressed by blocking CD226.
conclusionOur data revealed that the TIGIT and CD226 expression profiles could be used to identify functionally distinct subsets of CD4 T cells and TIGIT+CD226+ CD4 T cells is a significant subset in DM with enhanced frequency and effector function. This abnormal subset could be suppressed by blocking CD226, providing insight into the therapeutic target of the TIGIT/CD226 axis.
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