期刊
KIDNEY INTERNATIONAL
卷 99, 期 1, 页码 238-246出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.kint.2020.05.051
关键词
autoreactive T cells; lupus nephritis; SLE
资金
- Deutsche Forschungsgemeinschaft [Sonderforschungsbereich 650]
- Deutsche Gesellschaft fur Nephrologie
- Clinical Scientist Program of Charite - Universitatsmedizin Berlin
- Clinical Scientist Program of Charite - Berlin Institute of Health
Systemic lupus erythematosus is characterized by loss of tolerance towards nuclear antigens with autoreactive CD4(+) T cells implicated in disease pathogenesis. The frequencies of nuclear antigen specific CD4(+) T cells correlate with disease severity, and these cells produce multiple effector cytokines. These previously unrecognized characteristics support a role for nuclear antigen-specific CD4(+) T cells in systemic lupus erythematosus.
Systemic lupus erythematosus is a systemic and chronic autoimmune disease characterized by loss of tolerance towards nuclear antigens with autoreactive CD4(+) T cells implicated in disease pathogenesis. However, very little is known about their receptor specificity since the detection of human autoantigen specific CD4(+) T cells has been extremely challenging. Here we present an analysis of CD4(+) T cells reactive to nuclear antigens using two complementary methods: T cell libraries and antigenreactive T cell enrichment. The frequencies of nuclear antigen specific CD4(+) T cells correlated with disease severity. These autoreactive T cells produce effector cytokines such as interferon-gamma, interleukin-17, and interleukin-10. Compared to blood, these cells were enriched in the urine of patients with active lupus nephritis, suggesting an infiltration of the inflamed kidneys. Thus, these previously unrecognized characteristics support a role for nuclear antigen-specific CD4(+) T cells in systemic lupus erythematosus.
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