Impaired TNF/TNFR2 signaling enhances Th2 and Th17 polarization and aggravates allergic airway inflammation.

American journal of physiology. Lung cellular and molecular physiology

PubMedID: 28619762

Li XM, Chen X, Gu W, Guo YJ, Cheng Y, Peng J, Guo XJ. Impaired TNF/TNFR2 signaling enhances Th2 and Th17 polarization and aggravates allergic airway inflammation. Am J Physiol Lung Cell Mol Physiol. 2017;ajplung.00409.2016.
CD4+T cell differentiation plays an important role in allergic airway diseases. Tumor necrosis factor receptor 2 (TNFR2) has been shown to regulate CD4+T lymphocyte differentiation, but its role in allergic airway inflammation is not clear. Here we investigated the role of TNFR2 in allergic airway inflammation. Mouse model was generated by immunization with OVA and intranasal administration of TNFR2 antibody. Airway inflammation and CD4+T cell differentiation were measured in vivo and in vitro. Inhibited TNFR2 signaling aggravated airway inflammation and increased the expression of inflammatory cytokines (IL-4, IL-5, IL-17, and TNF-a) in serum and bronchoalveolar lavage fluid (BALF). Impaired TNFR2 signaling promoted Th2 and Th17 polarization but inhibited Th1 and CD4+CD25+ T cells differentiation in vivo. Furthermore, TNFR2 signaling inhibition promoted Th2 and Th17 polarization in vitro, which may through the activation of TNF receptor-associated factor 2 (TRAF2) and nuclear factor (NF)-?B signaling. Therefore, our findings indicate that impaired TNF/TNFR2 signaling enhances Th2 and Th17 polarization and aggravates allergic airway inflammation.