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
Notice bibliographique
Résumé
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.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».