2011 Fiscal Year Final Research Report
Investigation and therapeutic application of ICOS and ICOSL in systemic sclerosis
| Project/Area Number |
21591456
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Project Period (FY) |
2009 – 2011
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| Keywords | 強皮症 / 線維化 / ICOS / ICOSL / ブレオマイシン / 皮膚 / 肺 |
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| Research Abstract |
We assessed the roles of ICOS and ICOSL in tissue fibrosis by administering bleomycin intratracheally or intradermally into ICOS and/or ICOSL-deficient mice. The loss of ICOS attenuated fibrosis of lungs and skin, whereas deficiency of ICOSL aggravated it. Mice deficient in both ICOS and ICOSL also exhibited accelerated fibrosis, reflecting a dominant role for ICOSL over ICOS in this model. ICOSL expression on macrophages and B cells in bronchoalveolar fluids was significantly elevated in ICOS-deficient mice compared to wild type mice during this process. Thus, ICOSL expression levels on B cells and macrophages were inversely associated with the severity of tissue fibrosis. Our results indicate that ICOSL expression on antigen presenting cells plays a previously unknown regulatory role during the development of bleomycin-induced tissue fibrosis which is independent of the ICOS-ICOSL pathway.
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