Asthma is induced by intranasal coadministration of allergen and natural killer T-cell ligand in a mouse model

Plasticity of Invariant NKT Cell Regulation of Allergic Airway Disease Is Dependent on IFN-γ Production

“…These results share some features with previous studies indicating that activation of iNKT cells in the initial phase was critical to the development of allergic airway inflammation and AHR (39,40). Kim et al (39) demonstrated that aGalCer, coadministered intranasally with OVA on three consecutive days, led to the development of AHR and airway inflammation, whereas OVA priming alone did not result in airway inflammation and AHR.…”

Glycolipid activation of invariant T cell receptor + NK T cells is sufficient to induce airway hyperreactivity independent of conventional CD4 + T cells

“…In contrast, other investigators have found that coadministration of ␣-GalCer with antigen sensitizes mice to these antigens, thereby enhancing AHR (38,39). These seemingly contradictory results confirm that iNKT cells are critically involved in the regulation of AHR and indicate that the timing of activation of the iNKT cells dictates their role in AHR.…”

“…Because conventional CD4 ϩ T cells alone do not appear to induce AHR in mouse models of asthma (15,16), we suggest that in many forms of asthma, iNKT cells are synergistic with conventional CD4 ϩ T cells in the induction of allergic pulmonary inflammation. First, iNKT cells may become activated early on and, by releasing IL-4 and IL-13, boost the priming of allergenspecific conventional CD4 ϩ T cells (38,39). Second, we suggest that inflammation or pulmonary injury induced by allergen-specific Th2 cells may modify or uncover self-glycolipid antigens, which then activate iNKT (effector) cells that directly induce AHR.…”

“…These seemingly contradictory results confirm that iNKT cells are critically involved in the regulation of AHR and indicate that the timing of activation of the iNKT cells dictates their role in AHR. Thus, activation of iNKT cells can function as an adjuvant when iNKT cells are activated during the administration of protein antigen (38), can directly induce AHR when they are activated in the absence of other signals (Fig. 1), or can function to ''prevent'' the development of AHR, when they are rendered unresponsive (possibly anergic) at a critical time point by strong NKT cell activating agents (18).…”

Impact of T‐cell receptor Vβ haplotypes on the development of dermatitis in DS‐Nh mice: synergistic production of interleukin‐13 caused by staphylococcal enterotoxin C and peptide glycans from Staphylococcus aureus

“…However, there are two antithetic hypotheses on the relationship between NKT cells and allergic diseases. [42][43][44][45] The first suggests that NKT cells cause an allergic disease while the second suggests that NKT cells protect against allergic disease. Considering the results presented in this study, NKT cells may play a promotive role in the development of AD, but further investigation is needed to elucidate the possibility of these cells as a therapeutic target.…”