Hunger, R E; Müller, S; Laissue, J A; Hess, M W; Carnaud, C; Garcia, I; Mueller, C (1996). Inhibition of submandibular and lacrimal gland infiltration in nonobese diabetic mice by transgenic expression of soluble TNF-receptor p55. Journal of clinical investigation, 98(4), pp. 954-961. American Society for Clinical Investigation 10.1172/JCI118879
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Besides a prominent mononuclear cell infiltration of the islets of Langerhans, nonobese diabetic (NOD) mice also show massive cellular infiltrates of the submandibular and lacrimal glands concomitant with histological signs of tissue damage. To obtain insights into the mechanisms operative during the initiation and progression of tissue damage, we followed by in situ hybridization the appearance of cells containing mRNA of the gene encoding the proinflammatory cytokine TNF-alpha in the cellular infiltrates. Cells expressing TNF-alpha are mainly located in infiltrates, are absent in nonaffected glands, and are preferentially found among CD4 T cells. Secretion of TNF-alpha by gland-infiltrating cells was confirmed by an ELISPOT procedure. Direct evidence for an instrumental role of TNF-alpha in initiation and progression of submandibular and lacrimal gland infiltration is provided by the observed significant reduction in the extent of infiltration in nonobese diabetic mice transgenic for a soluble TNF receptor p55 fused to the Fc part of human IgG3. This protection from infiltration is paralleled by decreased expression of the adhesion molecules ICAM-1 and VCAM-1 in submandibular and lacrimal glands. These data suggest a central role of TNF-alpha in the initiation and progression of autoimmune tissue destruction of salivary glands and indicate beneficial effects of soluble TNF receptors in the treatment of organ-specific autoimmune diseases.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Service Sector > Institute of Pathology |
UniBE Contributor: |
Müller, Christoph (C) |
Subjects: |
500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health |
ISSN: |
0021-9738 |
Publisher: |
American Society for Clinical Investigation |
Language: |
English |
Submitter: |
Christoph Müller |
Date Deposited: |
22 Sep 2022 15:44 |
Last Modified: |
29 Mar 2023 23:38 |
Publisher DOI: |
10.1172/JCI118879 |
PubMed ID: |
8770867 |
BORIS DOI: |
10.48350/172958 |
URI: |
https://boris.unibe.ch/id/eprint/172958 |
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