Leptin/osteopontin axis contributes to enhanced T helper 17 type responses in allergic rhinitis.

Background: Recent studies suggest that T helper 17 (Th17) cell subset, a distinct pro-inflammatory CD4 +  T cell lineage, may play an important role in the pathophysiology of allergic rhinitis (AR). However, the regulation of Th17 response in allergic disease is not well characterized.

Methods: Thirty AR and 30 healthy children were enrolled. Serum leptin and OPN levels were measured, and their correlation with IL-17 expression was analyzed using enzyme-linked immunosorbent assay (ELISA). Th17 cell differentiation and cytokine production in peripheral blood mononuclear cell (PBMCs) stimulated by leptin and OPN and related inhibitors were analyzed by ELISA. AR mice models were also established to verify the effect of leptin and OPN on Th17 cell regulation. Immunoprecipitation was performed to explore the interaction between OPN and leptin in Th17 cells.

Results: Our results showed that elevated serum leptin and OPN in AR children were correlated with serum IL-17 level (r = .53, P < .01). The recombinant leptin and OPN enhanced Th17 responses from PBMCs synergistically through nuclear factor κB (NF-κB), mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) pathway and β3 integrin receptor. The AR mice showed as more severe Th17 responses and symptoms compared with control mice. Immunoprecipitation showed that OPN and leptin may interact with each other directly, and this process may be mediated by β3 integrin.

Conclusions: Our data provide evidence that upregulation of leptin and OPN promotes Th17 responses in AR, and this process may be achieved through NF-κB, MAPK, and JNK pathway and β3 integrin.