Altered Peripheral γδT Cell Profiles With Increased IL-17A Secretion in Patients With Eosinophilic Granulomatosis With Polyangiitis
Bibliographic record
Abstract
Abstract Rationale: Eosinophilic Granulomatosis with Polyangiitis (EGPA) is an autoimmune vasculitic disorder, often characterized by severe asthma and blood eosinophilia, with serum anti-neutrophil cytoplasmic antibody (ANCA) observed in 40% of cases. γδ T cells are unconventional lymphocytes with innate-like functions, capable of recognizing antigens directly. These cells have been implicated in autoimmune diseases, such as multiple sclerosis, where early IL-17 secretion from γδ T cells promotes Th17 cell activation (PMID: 31505409). In a mouse model of ANCA-associated vasculitis, IL-17A-secreting γδ T cells drive the development of ANCA-specific CD4 T cells (PMID: 28954887). This study assessed cytokine-secreting T cells, particularly γδ T cells, in the peripheral blood and sputum of patients with asthma and EGPA, compared to healthy controls. Methods: Peripheral blood mononuclear cells (PBMCs) and sputum samples were collected from EGPA (n=20, mean age: 57 ±14 years, 57% female, mean OCS dose: 5 mg/d), moderate-to-severe asthma (n=18, age: 58 ±12 years, 60% female, mean OCS dose: 3 mg/d), and healthy controls (n=54, age: 47 ±18 years, 67% female). T cell populations, including helper (CD4+), cytotoxic (CD8+), and γδ T cells, were analyzed by flow cytometry, along with exhaustion markers (EOMES, PD-1) and the Th1 transcription factor T-bet. Cytokine secretion was evaluated after a 4-hour stimulation of PBMCs with phorbol 12-myristate 13-acetate, ionomycin, and brefeldin A. Results: Peripheral γδ T cell frequencies were significantly reduced in both asthma and EGPA patients compared to healthy controls (p<0.01, Fig 1A). PD-1 expressing γδT cells was markedly higher in EGPA patients compared to healthy controls (p<0.01, Fig 1C). Upon stimulation, EGPA patients showed an increased proportion of IL-17A secreting γδT cells, a pro-inflammatory cytokine, compared to healthy controls (p<0.05, Fig 1D). IL-17A secretion was not significantly different in CD4+ and CD8+ T cells. Furthermore, there was no association between T cell populations and serum or sputum ANCA levels. No significant differences were observed in T cell populations from sputum samples across asthma, EGPA, and healthy controls (Fig 1B). Conclusion: This study reveals a distinct alteration in peripheral γδT cell profiles in patients with EGPA, characterized by a reduced frequency but increased IL-17A secretion. Elevated PD-1 expression further suggests a state of γδT cell exhaustion in EGPA, which may contribute to the autoimmune pathology and chronic inflammation observed in these patients. These insights into γδT cell dysregulation in EGPA highlight potential immune pathways that warrant further investigation.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 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) | 0.002 | 0.000 |
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".