Protective role of interferon gamma in murine antigen-induced arthritis
Bibliographic record
Abstract
In human rheumatoid arthritis interactions of immune cells with resident cells, especially synovial fibroblasts, play a crucial role in the perpetuation of inflammatory and destructive processes in affected joints. Apart from macrophages, Th cells are predominant in cell infiltrates, and Th cell responses are specified as Th1 type. As interferon gamma (IFN-γ) secreting Th1 cells are suspected to promote autoimmune diseases, there is the notion that a shift of a Th1 response towards a Th2 response might ameliorate arthritis. However, in different models and therapy studies conflicting results are described. Thus, we investigated the role of IFN-γ in murine antigen-induced arthritis (AIA), a model with homologies to human rheumatoid arthritis in terms of histopathology, chronicity and responses to several immunomodulatory drugs. AIA was evaluated in IFN-γ mice in comparison with C57BL/6 wild-type mice by clinical, histological and immunological parameters. Furthermore, Th cells isolated from immunised mice were separated according to their IFN-γ on the cell surface into IFN-γ and IFN-γ Th cells and than transferred into naive mice, which received at the same time a single injection of antigen (methylated bovine serum albumin) into the knee joint for arthritis induction. In cocultures with synovial fibroblasts, the stimulatory capacity of IFN-γ and IFN-γ Th cells was tested in vitro , analysing the levels of matrix metalloproteases, IL-6, and nitric oxide in supernatants. IFN-γ mice developed a more severe arthritis than wild-type mice with higher knee joint swelling, stronger acute inflammation and increased chronic joint destruction, even though IgG levels (total and methylated bovine serum albumin-specific) were reduced. Application of rIFN-γ ameliorates the severity of AIA in IFN-γ mice. Congruently, the transfer of IFN-γ Th cells from immunised wild-type mice into naive mice led to a more severe arthritis than the transfer of IFN-γ Th cells. Furthermore, IFN-γ Th cells had a stronger stimulatory capacity for matrix metalloproteases and IL-6 in synovial fibroblasts in vitro , whereas IFN-γ Th cells were more potent nitric oxide inducers. Inducing processes are mainly driven by direct cell contact. These experiments suggest a protective role of IFN-γ in the experimental arthritis model. The lack of IFN-γ in Th cells exerted a higher disease-promoting effect in vivo as well as a higher stimulatory capacitiy to synovial fibroblasts in vitro . The recent data generated in experimental models indicate a more complex role of IFN-γ in the pathogenesis of Th1-mediated autoimmune diseases than originally proposed.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".