Abstract: TH-PO0702
Dexamethasone Controls ILC2 GATA3 Expression but Not ILC2 Cell Number in Steroid-Dependent Nephrotic Syndrome in Relapse
Session Information
- Glomerular Diseases: Immunopathogenesis and Targeted Therapeutics
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Chan, Chang-Yien, National University of Singapore, Singapore, Singapore
- Lu, Liangjian, Khoo Teck Puat - National University Children's Medical Institute, Singapore, Singapore
- Quek, Li Ling, Khoo Teck Puat - National University Children's Medical Institute, Singapore, Singapore
- Teo, Sharon, Khoo Teck Puat - National University Children's Medical Institute, Singapore, Singapore
- Than, Mya, National University of Singapore, Singapore, Singapore
- Lau, Yew Weng Perry, National University of Singapore, Singapore, Singapore
- Ng, Kar Hui, National University of Singapore, Singapore, Singapore
- Yap, Hui Kim, National University of Singapore, Singapore, Singapore
Background
We have previously reported a predominant Th2 immune response in steroid-dependent nephrotic syndrome (SDNS). This study aimed to study ILC2s contribution to the Th2-biased phenotype in INS patients in relapse and their response to steroids.
Methods
14 patients with childhood-onset INS (relapse and remission) and 7 age-matched healthy controls were recruited. ILC2s were isolated through removal of CD19, CD4, CD8, CD14 followed by ILC2s selection (ILC2 isolation kit, Miltenyi). ILC2 culture supernatants were collected for cytokine measurement following 72h expansion with IL-33, IL-25, TSLP (10ng/ml) and IL-2 (20ng/ml). GATA3 expression levels were examined in ILC2s though incubation of PBMC with IL-33 (10ng/ml) for 72h, with or without Dexamethasone (Dex) (0.1µmol/ml). ILC subsets and GATA3 were analysed using flow cytometry, with ILC2s defined as CD45+Lin-CD127+CRTH2+. Statistical analysis was done using Mann-Whitney U tests and Wilcoxon signed-rank test for paired samples.
Results
INS patients in relapse had higher ILC2s levels compared to controls (19.0±2.2% vs 9.6±2.3%, P=0.01) with concomitant elevated production of type 2 (Th2) and Th2-related cytokines (IL-5, IL-13, IL-9, IL-10 and Eotaxin (P<0.04)). This was associated with higher GATA3 expression in ILC2s in SDNS patients compared to controls (18.13%±3.46% vs 2.50%±2.50%, P=0.02), which was not seen in SRNS patients (3.70%±3.70%, P>0.99), in keeping with Type 2 polarisation in steroid-dependent disease. Following remission, ILC2s levels were significantly decreased (P=0.01, paired). Dexamethasone incubation in relapsed SDNS patients resulted in downregulation of ILC2 GATA3 levels (mean difference 13.96%±3.21%, P=0.02, paired), but paradoxically increased ILC2 cell numbers (mean difference 5.8±1.1%, P<0.001).
Conclusion
ILC2s are expanded with greater Th2 cytokine production in relapse compared to healthy controls, associated with GATA3 expression in steroid-dependent disease. Steroid therapy constraints ILC2 GATA3 expression and Th2 polarisation, but does not effectively decrease ILC2 cell number directly. ILC2 expansion may instead be reversed indirectly by the effects of steroids on other cell types and mediators in vivo, which can serve as additional therapeutic targets.