Interferon α2 and interferon γ induce the degranulation independent production of VEGF‐A and IL‐1 receptor antagonist and other mediators from human mast cells
Bibliographic record
Abstract
BACKGROUND: Mast cells are resident immune effector cells, often studied in the context of allergic disease. Found in substantial numbers at sites of potential infection they are increased at sites of angiogenesis and can be pivotal for the sensing and clearance of a variety of pathogens. Interferons (IFNs) are cytokines that are critical for host defence against intracellular pathogens. Increased levels of IFNs are observed during viral infection and in autoimmune diseases. IFNs are also widely used therapeutically and have been examined in the therapy of severe asthma. OBJECTIVE: To define the selective human mast cell cytokine and chemokine response following activation with type I or type II IFN's. METHODS: The ability of both IFNα2 and IFNγ to induce cytokine production by human cord blood-derived mast cells was examined in vitro. Cytokine and chemokine production at 6 and 24 h was assessed by multiplex protein analysis. Degranulation was assessed by β-hexosaminidase release. Mast cells were also treated with reovirus or respiratory syncytial virus and their production of CXCL10, IL-1 receptor antagonist (IL-1Ra), and vascular endothelial growth factor (VEGF) examined after 24 h. RESULTS: In addition to increased expression of classical IFN response genes, such as CXCL10, small but significant increases in CCL5 and IL-17 production were observed following IFN activation. Notably, human mast cells produced both VEGF and IL-1Ra in a dose dependent manner. These responses occurred in the absence of mast cell degranulation by a mechanism consistent with classical IFN signaling. Both reovirus and respiratory syncytial virus infection of mast cells, were also associated with IFN-dependent IL-1Ra expression. CONCLUSION AND CLINICAL RELEVANCE: Our findings demonstrate that IFNs have profound impact on cytokine and chemokine expression by human mast cells, alone or in the context of viral infection. Mast cell VEGF and IL-1Ra responses to IFNs could impact the regulation of local inflammatory responses and subsequent tissue remodeling.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 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 source (direct Gemma or distilled Codex), 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".