Edited by: Hans-Uwe Simon
An important role of tumor necrosis factor receptor-2 on natural killer T cells on the development of dsRNA-enhanced Th2 cell response to inhaled allergens
Article first published online: 6 NOV 2013
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Volume 69, Issue 2, pages 186–198, February 2014
How to Cite
An important role of tumor necrosis factor receptor-2 on natural killer T cells on the development of dsRNA-enhanced Th2 cell response to inhaled allergens. Allergy 2014; 69: 186–198., , , , , , , , , .
- Issue published online: 27 JAN 2014
- Article first published online: 6 NOV 2013
- Manuscript Accepted: 14 SEP 2013
- Korea Ministry of Health & Welfare, Republic of Korea. Grant Number: HI 13C 0040-010013
- Th2 sensitization;
- TNF receptor-2;
- type I natural killer T cells
Recent evidence indicates that TNF-α is a key mediator of the development of dsRNA-enhanced Th2 cell response to inhaled allergens. Natural killer T (NKT) cells may be a candidate source of Th2-polarizing cytokines.
The objective of this study was to evaluate the role of lung NKT cells on the development of TNF-α-mediated Th2 cell response.
A virus-associated asthma mouse model was generated by the administration of ovalbumin (OVA, 75 μg) and poly[I:C] (0.1 μg). Role of NKT and type I NKT cells was evaluated using CD1d- and Jα18-deficient mice. TNF-α receptors (TNFRs) were antagonized by using TNFR blocking peptides.
The number of infiltrated NKT cells was increased in a virus-associated asthma mouse model. Increase in Th2 and Th17 cytokine levels in wild-type mice were abolished in both CD1d- and Jα18-deficient mice. In vitro co-culture experiments with alveolar macrophages and NKT cells showed that TNF-α produced by macrophages in the presence of poly[I:C] acts on NKT cells, inducing production of Th2-polarizing cytokines. Moreover, the induction of Th2-polarizing cytokines by poly[I:C] or recombinant TNF-α was impaired in both CD1d- and Jα18-deficient mice and that the above effect was reversed by a TNF-α receptor-2 (TNFR2) blocking peptide, but not by a TNFR1 blocker.
These findings suggest that NKT cells play a key role in the development of Th2 cell response to inhaled allergens and that TNF-α produced by alveolar macrophages induces Th2 cell response, via TNFR2 on NKT cells.