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Arthritis Rheum. 2010 Jun;62(6):1723-32. doi: 10.1002/art.27428.

Inducible costimulator ligand regulates bleomycin-induced lung and skin fibrosis in a mouse model independently of the inducible costimulator/inducible costimulator ligand pathway.

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1
Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.

Abstract

OBJECTIVE:

Systemic sclerosis is a connective tissue disease characterized by fibrosis of the skin and internal organs, including the lungs. Inducible costimulator (ICOS), which is expressed on activated T cells, and its ligand ICOSL, which is expressed on antigen-presenting cells, have been considered a single receptor-ligand pair. Although the ICOS/ICOSL pathway is known to play various roles in adaptive immunity, its roles in innate immunity and tissue fibrosis remain unknown.

METHODS:

We assessed the roles of ICOS and ICOSL in tissue fibrosis by administering bleomycin intratracheally or intradermally into mice deficient in ICOS and/or ICOSL. Tissue fibrosis was evaluated by histologic or biochemical examination.

RESULTS:

ICOS deficiency attenuated the lung and skin fibrosis, whereas ICOSL deficiency aggravated it. Mice deficient in both ICOS and ICOSL exhibited accelerated fibrosis, reflecting a dominant role of ICOSL over ICOS in this model. Interestingly, ICOSL expression on macrophages and B cells derived from bronchoalveolar lavage fluid was significantly elevated in ICOS-deficient mice as compared with wild-type mice during this process. Thus, the levels of ICOSL expression on B cells and macrophages were inversely associated with the severity of tissue fibrosis.

CONCLUSION:

Our results indicate that ICOSL expression on antigen-presenting cells plays a previously unknown regulatory role during the development of bleomycin-induced tissue fibrosis that is independent of the ICOS/ICOSL pathway. Further studies will be needed to clarify the roles of ICOS and ICOSL in the development of systemic sclerosis.

PMID:
20191584
DOI:
10.1002/art.27428
[Indexed for MEDLINE]
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