Thymic Stromal Lymphopoietin May Induce Steroid Resistance in Minimal Change Disease

Minimal change disease (MCD) is one of the causes of idiopathic nephrotic syndrome, and 40% of patients have allergic diseases. About 30% of MCD patients become resistant to steroid after a long period of steroid therapy; however, the mechanism of steroid resistance is unclear. Thymic stromal lymphopoietin (TSLP), an epithelial cytokine, is known to be associated with steroid-resistant allergic disease. Experiments using mouse models of asthma suggest that TSLP-mediated phosphorylation of signal transducer and activator of transcription 5 (STAT5) binds to corticosteroid receptors, resulting in steroid resistance. In the present study, we aim to investigate whether TSLP is involved in steroid resistance in patients with MCD. We compared serum TSLP levels in patients with MCD (n = 26) and healthy controls (n = 13). The cultured podocytes were used to investigate whether TSLP attenuates the podocyte-protective effect of dexamethasone (DEX) and whether the administration of a TSLP-neutralising antibody abolishes TSLP-induced steroid resistance. The level of serum TSLP in patients with MCD was significantly higher than that in healthy controls (p < 0.05). Of note, in patients with MCD, serum TSLP levels significantly elevated at recurrence (p < 0.05). In vitro, DEX protected podocytes from Adriamycin-induced injury. The protective effect of DEX on podocytes was attenuated by co-culture with TSLP (p < 0.01). However, treatment with TSLP neutralising antibody improved TSLP-induced steroid resistance (p < 0.001). We also found that TSLP induces STAT5 activation in podocytes, which is blocked by TSLP-neutralising antibodies. TSLP may be involved in steroid resistance via the STAT5 pathway in podocytes.