Disease-dependent local IL-10 production ameliorates collagen induced arthritis in mice.
Rheumatoid arthritis (RA) is a chronic destructive autoimmune disease characterised by periods of flare and remission. Today's treatment is based on continuous immunosuppression irrespective of the patient's inflammatory status. When the disease is in remission the therapy is withdrawn but...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3500327?pdf=render |
| _version_ | 1819276547857580032 |
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| author | Louise Henningsson Tove Eneljung Pernilla Jirholt Sara Tengvall Ulf Lidberg Wim B van den Berg Fons A van de Loo Inger Gjertsson |
| author_facet | Louise Henningsson Tove Eneljung Pernilla Jirholt Sara Tengvall Ulf Lidberg Wim B van den Berg Fons A van de Loo Inger Gjertsson |
| author_sort | Louise Henningsson |
| collection | DOAJ |
| description | Rheumatoid arthritis (RA) is a chronic destructive autoimmune disease characterised by periods of flare and remission. Today's treatment is based on continuous immunosuppression irrespective of the patient's inflammatory status. When the disease is in remission the therapy is withdrawn but withdrawal attempts often results in inflammatory flares, and re-start of the therapy is commenced when the inflammation again is prominent which leads both to suffering and increased risk of tissue destruction. An attractive alternative treatment would provide a disease-regulated therapy that offers increased anti-inflammatory effect during flares and is inactive during periods of remission. To explore this concept we expressed the immunoregulatory cytokine interleukin (IL)-10 gene under the control of an inflammation dependent promoter in a mouse model of RA - collagen type II (CII) induced arthritis (CIA). Haematopoetic stem cells (HSCs) were transduced with lentiviral particles encoding the IL-10 gene (LNT-IL-10), or a green fluorescence protein (GFP) as control gene (LNT-GFP), driven by the inflammation-dependent IL-1/IL-6 promoter. Twelve weeks after transplantation of transduced HSCs into DBA/1 mice, CIA was induced. We found that LNT-IL-10 mice developed a reduced severity of arthritis compared to controls. The LNT-IL-10 mice exhibited both increased mRNA expression levels of IL-10 as well as increased amount of IL-10 produced by B cells and non-B APCs locally in the lymph nodes compared to controls. These findings were accompanied by increased mRNA expression of the IL-10 induced suppressor of cytokine signalling 1 (SOCS1) in lymph nodes and a decrease in the serum protein levels of IL-6. We also found a decrease in both frequency and number of B cells and serum levels of anti-CII antibodies. Thus, inflammation-dependent IL-10 therapy suppresses experimental autoimmune arthritis and is a promising candidate in the development of novel treatments for RA. |
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| id | doaj.art-78593b0e54b94fc6a8931f498b1b8e2b |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T23:41:58Z |
| publishDate | 2012-01-01 |
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| series | PLoS ONE |
| spelling | doaj.art-78593b0e54b94fc6a8931f498b1b8e2b2022-12-21T17:25:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01711e4973110.1371/journal.pone.0049731Disease-dependent local IL-10 production ameliorates collagen induced arthritis in mice.Louise HenningssonTove EneljungPernilla JirholtSara TengvallUlf LidbergWim B van den BergFons A van de LooInger GjertssonRheumatoid arthritis (RA) is a chronic destructive autoimmune disease characterised by periods of flare and remission. Today's treatment is based on continuous immunosuppression irrespective of the patient's inflammatory status. When the disease is in remission the therapy is withdrawn but withdrawal attempts often results in inflammatory flares, and re-start of the therapy is commenced when the inflammation again is prominent which leads both to suffering and increased risk of tissue destruction. An attractive alternative treatment would provide a disease-regulated therapy that offers increased anti-inflammatory effect during flares and is inactive during periods of remission. To explore this concept we expressed the immunoregulatory cytokine interleukin (IL)-10 gene under the control of an inflammation dependent promoter in a mouse model of RA - collagen type II (CII) induced arthritis (CIA). Haematopoetic stem cells (HSCs) were transduced with lentiviral particles encoding the IL-10 gene (LNT-IL-10), or a green fluorescence protein (GFP) as control gene (LNT-GFP), driven by the inflammation-dependent IL-1/IL-6 promoter. Twelve weeks after transplantation of transduced HSCs into DBA/1 mice, CIA was induced. We found that LNT-IL-10 mice developed a reduced severity of arthritis compared to controls. The LNT-IL-10 mice exhibited both increased mRNA expression levels of IL-10 as well as increased amount of IL-10 produced by B cells and non-B APCs locally in the lymph nodes compared to controls. These findings were accompanied by increased mRNA expression of the IL-10 induced suppressor of cytokine signalling 1 (SOCS1) in lymph nodes and a decrease in the serum protein levels of IL-6. We also found a decrease in both frequency and number of B cells and serum levels of anti-CII antibodies. Thus, inflammation-dependent IL-10 therapy suppresses experimental autoimmune arthritis and is a promising candidate in the development of novel treatments for RA.http://europepmc.org/articles/PMC3500327?pdf=render |
| spellingShingle | Louise Henningsson Tove Eneljung Pernilla Jirholt Sara Tengvall Ulf Lidberg Wim B van den Berg Fons A van de Loo Inger Gjertsson Disease-dependent local IL-10 production ameliorates collagen induced arthritis in mice. PLoS ONE |
| title | Disease-dependent local IL-10 production ameliorates collagen induced arthritis in mice. |
| title_full | Disease-dependent local IL-10 production ameliorates collagen induced arthritis in mice. |
| title_fullStr | Disease-dependent local IL-10 production ameliorates collagen induced arthritis in mice. |
| title_full_unstemmed | Disease-dependent local IL-10 production ameliorates collagen induced arthritis in mice. |
| title_short | Disease-dependent local IL-10 production ameliorates collagen induced arthritis in mice. |
| title_sort | disease dependent local il 10 production ameliorates collagen induced arthritis in mice |
| url | http://europepmc.org/articles/PMC3500327?pdf=render |
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