期刊
JOURNAL OF IMMUNOLOGY
卷 184, 期 7, 页码 3639-3647出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0903943
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资金
- National Institutes of Health [R37 AI40312, DPI OD00329]
- University of California at San Francisco-Gladstone Institute of Virology and Immunology Center for AIDS Research [P30 MH59037]
- University of California at San Francisco Clinical and Translational Research Institute Clinical Research Center [UL1 RR024131]
- Harvey V. Bemeking Living Trust
- Human Frontier Science Program
- National Institute of Arthritis and Musculoskeletal and Skin Diseases
- Academic Rheumatology
- Rosalind Russell Arthritis Center
- NATIONAL CENTER FOR RESEARCH RESOURCES [UL1RR024131] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [P30AI027763, R37AI040312] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [P30MH059037] Funding Source: NIH RePORTER
- OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH [DP1OD000329] Funding Source: NIH RePORTER
CD4(+)FoxP3(+) regulatory T cells (T-reg) play a critical role in maintaining self-tolerance and inhibiting autoimmune disease. Despite being a major focus of modern immunological investigation, many aspects of T-reg biology remain unknown. In a screen for novel candidate genes involved in human T-reg function, we detected the expression of an autoimmune susceptibility gene, FcRL3, in T-reg but not in conventional CD4(+) T cells. FcRL3 is an orphan receptor of unknown function with structural homology to classical Fc receptors. Numerous genetic studies have demonstrated a link between a single nucleotide polymorphism, in the FCRL3 promoter and both overexpression of FcRL3 and autoimmune diseases such as rheumatoid arthritis. Given the critical role of T-reg in suppressing autoimmunity, we sought to ascertain how expression of FcRL3 relates to the phenotype, differentiation, and function of T-reg. We show in this study that FcRL3 is expressed on a population of thymically derived T-reg that exhibits a memory phenotype and high levels of programmed cell death-1. Purified FcRL3(+) T-reg are less responsive to antigenic stimulation in the presence of IL-2 than their FcRL3(-) counterparts, despite intact proximal and distal IL-2 signaling as determined by phosphorylation of Stat-5 and upregulation of Bcl2. In vitro suppression assays demonstrated that FcRL3(+) T-reg have reduced capacity to suppress the proliferation of effector T cells. These data suggest that FcRL3 expression is associated with T-reg dysfunction that may, in turn, contribute to the loss of self-tolerance and the development of autoimmunity. The Journal of Immunology, 2010, 184: 3639-3647.
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