Gene Therapy Induces Antigen-Specific Tolerance in Experimental Collagen-Induced Arthritis
2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 5, e0154630Article in journal (Refereed) PublishedText
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 naive 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.
Place, publisher, year, edition, pages
2016. Vol. 11, no 5, e0154630
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-298679DOI: 10.1371/journal.pone.0154630ISI: 000376576700014PubMedID: 27159398OAI: oai:DiVA.org:uu-298679DiVA: diva2:947140