Thymic Stromal Lymphopoietin May Induce Steroid Resistance in Minimal Change Disease.

Abstract

Aim: 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.

Methods: 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.

Results: 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.

Conclusion: TSLP may be involved in steroid resistance via the STAT5 pathway in podocytes.