Tengvall, S;
Eneljung, T;
Jirholt, P;
Turesson, O;
Wing, K;
Holmdahl, R;
Kihlberg, J;
... Gjertsson, I; + view all
(2016)
Gene Therapy Induces Antigen-Specific Tolerance in Experimental Collagen-Induced Arthritis.
PLoS ONE
, 11
(5)
, Article e0154630. 10.1371/journal.pone.0154630.
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Abstract
Here, we investigate induction of immunological tolerance by lentiviral based gene therapy in a mouse model of rheumatoid arthritis, collagen II-induced arthritis (CIA). Targeting the expression of the collagen type II (CII) to antigen presenting cells (APCs) induced antigen-specific tolerance, where only 5% of the mice developed arthritis as compared with 95% of the control mice. In the CII-tolerized mice, the proportion of Tregs as well as mRNA expression of SOCS1 (suppressors of cytokine signaling 1) increased at day 3 after CII immunization. Transfer of B cells or non-B cell APC, as well as T cells, from tolerized to naïve mice all mediated a certain degree of tolerance. Thus, sustainable tolerance is established very early during the course of arthritis and is mediated by both B and non-B cells as APCs. This novel approach for inducing tolerance to disease specific antigens can be used for studying tolerance mechanisms, not only in CIA but also in other autoimmune diseases.
| Type: | Article |
|---|---|
| Title: | Gene Therapy Induces Antigen-Specific Tolerance in Experimental Collagen-Induced Arthritis |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0154630 |
| Publisher version: | https://doi.org/10.1371/journal.pone.0154630 |
| Language: | English |
| Additional information: | © 2016 Tengvall et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| Keywords: | Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, Regulatory T-Cells, II Collagen, B-Cells, Autoimmune Arthritis, Immune-Responses, Dendritic Cells, Transgenic Mice, Self-Tolerance, Induction, Suppression |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10050824 |
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