Title |
Anti-TNF drives regulatory T cell expansion by paradoxically promoting membrane TNF–TNF-RII binding in rheumatoid arthritis
|
---|---|
Published in |
The Journal of Experimental Medicine, June 2016
|
DOI | 10.1084/jem.20151255 |
Pubmed ID | |
Authors |
Dao Xuan Nguyen, Michael R. Ehrenstein |
Abstract |
The interplay between inflammatory and regulatory pathways orchestrates an effective immune response that provides protection from pathogens while limiting injury to host tissue. Tumor necrosis factor (TNF) is a pivotal inflammatory cytokine, but there is conflicting evidence as to whether it boosts or inhibits regulatory T cells (T reg cells). In this study, we show that the therapeutic anti-TNF antibody adalimumab, but not the soluble TNF receptor etanercept, paradoxically promoted the interaction between monocytes and T reg cells isolated from patients with rheumatoid arthritis (RA). Adalimumab bound to monocyte membrane TNF from RA patients and unexpectedly enhanced its expression and its binding to TNF-RII expressed on T reg cells. As a consequence, adalimumab expanded functional Foxp3(+) T reg cells equipped to suppress Th17 cells through an IL-2/STAT5-dependent mechanism. Our data not only highlight the beneficial effect of membrane TNF on T reg cell numbers during chronic inflammation, but in addition reveal how a therapeutic antibody that is thought to act by simply blocking its target can enhance the regulatory properties of this proinflammatory cytokine. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 12 | 32% |
United Kingdom | 3 | 8% |
Ireland | 2 | 5% |
Italy | 1 | 3% |
Netherlands | 1 | 3% |
Venezuela, Bolivarian Republic of | 1 | 3% |
Malaysia | 1 | 3% |
Japan | 1 | 3% |
Canada | 1 | 3% |
Other | 4 | 11% |
Unknown | 10 | 27% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 23 | 62% |
Scientists | 9 | 24% |
Science communicators (journalists, bloggers, editors) | 5 | 14% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 156 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 29 | 19% |
Researcher | 26 | 17% |
Student > Bachelor | 18 | 12% |
Student > Master | 18 | 12% |
Other | 15 | 10% |
Other | 24 | 15% |
Unknown | 26 | 17% |
Readers by discipline | Count | As % |
---|---|---|
Immunology and Microbiology | 36 | 23% |
Medicine and Dentistry | 27 | 17% |
Biochemistry, Genetics and Molecular Biology | 20 | 13% |
Agricultural and Biological Sciences | 18 | 12% |
Pharmacology, Toxicology and Pharmaceutical Science | 11 | 7% |
Other | 16 | 10% |
Unknown | 28 | 18% |