| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥240,000)
Fiscal Year 2007: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
We examined immunohistochemically roles of salivary gland cells as antigen presenting cells in pathogenesis of Sjogren's syndrome using autoimmune model mouse, MRL/lpr mice, and control mice, MRU+ mice, MRL/+ mice, in our present. Study. 5-month-old mice of each strain were sacrificed by anesthesia overdose followed by exsanguinations. Submandibular glands were removed fixed in 10% buffered formalin, and embedded in paraffin. Paraffin-embedded tissue sections (3μm) were immunostained against costimulatory factors, ie. CD80, CD8G, 4-1BB ligand, OX40 ligand, GITR ligand, which are related to autoreactive T cells activation provoking autoimmune responses, using streptoavidin- biotin method. Additionally, immunohistochemical localization of Foxp3, which is one of regulatory T cell markers and a transcription factor, was explored. The submandibular gland specimens of MRL/lpr mice showed intense expression of these four cistimulatory factors in ductal cells. However, the immunolocalizations of these ligands in MRL/+ mice were weak and not convincing.
Furthermore, we showed that infiltrating inflammatory cells were expanding extensively in submandibular gland specimens where all four costimulatory factors were localized. It has been clarified that some costimulatory factors reciprocally potentiate their functions, for example CD80 and OX40 ligand, 4-1BB ligand and CD80 or CD86, 4-1BB and OX40, and CD28 and GYM. Therefore, the synergy of four costimulatory factors possibly contributed to intensive inflammatory cell infiltration in autoimmune sialoadenitis of MRL/lpr mice.
Taken together our present study indicates that salivary gland ductal cells that playa pivotal role as antigen presenting cells through upregulated expression of these 5 costimulatory factors has the association with the development of Sjogren's syndrome- like sialadenitis in MRL/lpr mice.
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