Patients With Cutaneous Graft Versus Host Disease Exhibit Reduced Production Of IL-17
Bibliographic record
Abstract
It is well recognized that T cells are the principal orchestrators of graft versus host disease (GVHD). Historically, IFN-γ producing Th1 cells have been implicated in the pathogenesis of acute GVHD (aGVHD) whereas Th2 cells have been thought to be involved in the pathogenesis of chronic GVHD (cGVHD). The recent discovery of a distinct lineage of IL-17 producing Th17 cells, thought to be the major perpetrators in a number of inflammatory and autoimmune disorders, has prompted re-evaluation of the Th1/Th2 paradigm of GVHD. Studies in IL-17 deficient mice have shown conflicting results with IL-17 having both a protective or deleterious effect, whereas transplantation of purified Th17 cells causes GVHD-related tissue damage with a predilection for the skin and lungs. In this study we aimed to determine whether Th17 cells play a role in the pathogenesis of human GVHD. 37 patients undergoing allogeneic SCT were included in this study. Peripheral blood samples were taken prior to transplant and weekly until day +100. To assess if Th17 cells are involved in cGVHD, further samples were taken at 6 months and 1 year. Peripheral blood mononuclear cells were stimulated with PMA/Ionomycin and the lymphocytes were assessed for the intracellular expression of IL-17 and IL-22. In parallel, plasma was analysed for IL-17 production. We found the frequency of IL-17 and IL-22 producing cells was no higher in the 21 patients with aGVHD than the 16 patients without GVHD either at the onset of, or one week prior to aGVHD onset. Accordingly, the concentration of IL-17 in the plasma did not differ between the two groups. IL-17 producing cells and plasma levels were not elevated in patients who developed cGVHD. To exclude that circulating Th17 cells were not identified because of marginalization from the blood into tissues, we isolated T cells from the skin of patients with aGVHD (n=5) and cGVHD (n=7) and tested them for their capacity to produce Th17 associated cytokines. Interestingly, in patients with either acute or chronic GVHD, we found a population of cells that produced IL-22 but not IL-17 or IFN-γ. In accordance with this finding, the expression of CCR6, a marker for Th17 cells, was significantly lower in patients with GVHD. Our findings suggest that in humans, Th17 do not appear to contribute to the pathophysiology of GVHD, however in keeping with recent reports, there appears to be a distinct IL-22 producing population that may be important in skin pathology.
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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 | 0.001 |
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.005 | 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".