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Expansion of circulating peripheral TIGIT+CD226+ CD4 T cells with enhanced effector functions in dermatomyositis. 2021

Wenli Li, and Chuiwen Deng, and Hanbo Yang, and Xin Lu, and Shanshan Li, and Xia Liu, and Fang Chen, and Lida Chen, and Xiaoming Shu, and Lu Zhang, and Qingyan Liu, and Guochun Wang, and Qinglin Peng
Department of Rheumatology, China-Japan Friendship Hospital, Ying Hua East Road, Chao Yang District, Beijing, 100029, People's Republic of China.

T 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. We 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. Four 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. Our 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.

UI MeSH Term Description Entries
D011971 Receptors, Immunologic Cell surface molecules on cells of the immune system that specifically bind surface molecules or messenger molecules and trigger changes in the behavior of cells. Although these receptors were first identified in the immune system, many have important functions elsewhere. Immunologic Receptors,Immunologic Receptor,Immunological Receptors,Receptor, Immunologic,Receptors, Immunological
D003882 Dermatomyositis A subacute or chronic inflammatory disease of muscle and skin, marked by proximal muscle weakness and a characteristic skin rash. The illness occurs with approximately equal frequency in children and adults. The skin lesions usually take the form of a purplish rash (or less often an exfoliative dermatitis) involving the nose, cheeks, forehead, upper trunk, and arms. The disease is associated with a complement mediated intramuscular microangiopathy, leading to loss of capillaries, muscle ischemia, muscle-fiber necrosis, and perifascicular atrophy. The childhood form of this disease tends to evolve into a systemic vasculitis. Dermatomyositis may occur in association with malignant neoplasms. (From Adams et al., Principles of Neurology, 6th ed, pp1405-6) Polymyositis-Dermatomyositis,Dermatomyositis, Adult Type,Dermatomyositis, Childhood Type,Dermatopolymyositis,Juvenile Dermatomyositis,Juvenile Myositis,Adult Type Dermatomyositis,Childhood Type Dermatomyositis,Dermatomyositis, Juvenile,Myositis, Juvenile,Polymyositis Dermatomyositis
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000945 Antigens, Differentiation, T-Lymphocyte Antigens expressed on the cell membrane of T-lymphocytes during differentiation, activation, and normal and neoplastic transformation. Their phenotypic characterization is important in differential diagnosis and studies of thymic ontogeny and T-cell function. Antigens, Differentiation, T-Cell,Differentiation Antigens, T-Cell,L3T4 Antigens,Leu Antigens, T-Lymphocyte,T-Cell Differentiation Antigens,T-Lymphocyte Differentiation Antigens,T6 Antigens,Antigens, Differentiation, T Lymphocyte,Differentiation Antigens, T Lymphocyte,Antigens, L3T4,Antigens, T-Cell Differentiation,Antigens, T-Lymphocyte Differentiation,Antigens, T-Lymphocyte Leu,Antigens, T6,Differentiation Antigens, T Cell,Differentiation Antigens, T-Lymphocyte,Leu Antigens, T Lymphocyte,T Cell Differentiation Antigens,T Lymphocyte Differentiation Antigens,T-Lymphocyte Leu Antigens
D015496 CD4-Positive T-Lymphocytes A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes. T4 Cells,T4 Lymphocytes,CD4-Positive Lymphocytes,CD4 Positive T Lymphocytes,CD4-Positive Lymphocyte,CD4-Positive T-Lymphocyte,Lymphocyte, CD4-Positive,Lymphocytes, CD4-Positive,T-Lymphocyte, CD4-Positive,T-Lymphocytes, CD4-Positive,T4 Cell,T4 Lymphocyte
D016176 T-Lymphocyte Subsets A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells. T-Cell Subset,T-Cell Subsets,T-Lymphocyte Subset,Subset, T-Cell,Subset, T-Lymphocyte,Subsets, T-Cell,Subsets, T-Lymphocyte,T Cell Subset,T Cell Subsets,T Lymphocyte Subset,T Lymphocyte Subsets

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