REDUCED FREQUENCY OF CIRCULATING INTERLEUKIN-16 EXPRESSING CD4+AND CD8+T CELLS ASSOCIATE WITH INCREASED URINARY IL16 LEVELS AND PROMOTE TH1 AND CD8+T CELL MIGRATION IN LUPUS PATIENTS
Bibliographic record
Abstract
PT020 / #451 Topic: AS16 - Lupus Nephritis-Pathogenesis POSTER TOUR 04: SLE PATHOGENESIS 24-05-2025 10:00 AM - 10:20 AM Background/Purpose Cytokine dysregulation is recognized as key factor in the development of several autoimmune diseases. Data suggests interleukin-16 (IL16) is involved in the pathogenesis of systemic lupus erythematosus (SLE) and especially in lupus nephritis (LN). Yet, information on the cellular source of IL16 as well as its pathogenic relevance is scarce. Elucidating IL16- producing and secreting cells and their association with SLE manifestations may provide more precise disease biomarker and guide in developing new therapeutic interventions. Methods Thirty-four SLE patients and 15 healthy controls (HCs) were included. Among lupus patients, 16 had LN (48%). In patient cohort, 32 plasma (LN, n = 13 and non-LN, n = 19) and 21 urine (LN, n = 10 and non-LN, n = 11) samples were collected for IL16 measurement by ELISA. Data is represented as median and interquartile range (IQR). Ex vivo IL16-expressing cells were analyzed by spectral flow cytometry. Correlation analysis between IL16-expressing cells and plasma/urine IL16 levels and clinical parameters was performed. The capacity of IL16 to induce T cell migration was evaluated in SLE patients (n = 2) and HCs (n = 2) using a chemotaxis assay. Results Patients were mainly females (95%), of median age 41 (31-49) years. We first proceeded to detect IL16 at cellular level without any stimulation, finding IL16 at intracellular level while no surface expression was detected. Compared with HCs, a decreased frequency of IL16-expressing cells within CD4+T, CD8+T, B and NK cells was observed in SLE patients. Through multiparameter flow cytometric analysis, we observed a reduction of IL16-expressing cells from several B cell subsets which included plasmablasts (CD19+CD27 high CD38 high ), double negative (CD19+CD27-IgD-) and naive (CD19+CD27-IgD+) in patients. Similarly, fewer IL16-expressing T helper1 cells (Th1: CXCR3+CCR6-) were detected in patients. LN patients showed decreased IL16-expression in total CD4+T cells as well as in their subsets including Th1 and regulatory T (Treg: CD25+CD127-), compared to non-LN. Concerning plasma (p-) and urine (u-) IL16, we found elevated p-IL16 levels in patients vs HCs, while increased u-IL16 was only detected in LN subgroup. Additionally, a significant negative correlation between circulating IL16-expressing CD4+ ( r = -0.52, p =0.03) and CD8+ ( r = -0.46, p =0.04) T cells with u-IL16 was observed, suggesting their IL16-secreting roles. The u-IL16 levels of LN patients showed positive correlation with SLEDAI-2K index ( r = 0.85, p =0.003) and negative with C4 levels ( r = -0.66, p =0.04). We further explored the migratory role of IL16 by in vitro assays which showed that IL16 could preferentially induce T cell migration in both patients and HCs. Intriguingly, an increased proportion of transmigrated CD8+T cells was observed in patients, while HCs showed increased transmigrating CD4+T cells. Among transmigrated CD4+T cell subsets, Th1 cells were enriched after IL16 stimulation. The addition of IL16 blocking antibody resulted in a diminished frequency of transmigrated T cells with significantly decreased proportion of CD8+T cells which was observed in SLE patients. Conclusions Both B and T cell compartments in SLE patients show reduced positivity for IL16 expression. Reduced numbers of circulating IL16-expressing CD4+ and IL16-expressing CD8+T cells in patients appear associated with u-IL16 levels, suggesting their IL16 secreting abilities. The biological effect of IL16 in inducing migratory responses in Th1 and CD8+T cells in SLE may suggest pivotal role in the recruitment of pathogenic T cells. Therefore, targeting the IL16 might be an alternative strategy for targeted therapy.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.000 | 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 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".