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Cell-penetrating peptides (CPPs) or protein transduction domains (PTDs) are peptides that have the ability to efficiently traverse cellular membranes, either alone or in association with molecular cargo. Several naturally occurring [...]

Background: Th2 immune responses are linked primarily to mild and moderate asthma, while Th17 cells, Interleukin-17A (IL-17) and neutrophilia have been implicated in more severe forms of disease. How Th2-dependent allergic reactions are influenced by Th17 and IL-17-Υδ T cells is poorly understood. In murine models, under some conditions, IL-17 promotes Th2-biased airway inflammatory responses. However, IL-17-Υδ T cells have been implicated in the inhibition and resolution of allergic airway inflammation and hyperresponsiveness (AHR). Methods: We compared airway responses in Balb/c mice sensitized to OVA with (and without) a Th2-skewing aluminum-based adjuvant and the IL-17 skewing, complete Freund's adjuvant (CFA). AHR was measured invasively by flexiVent, while serum OVA-IgE was quantified by an enzyme immunoassay. Airway inflammatory and cytokine profiles, and cellular sources of IL-17 were assessed from bronchoalveolar lavage and/or lungs. The role of Υδ T cells in these responses was addressed in OVA/CFA sensitized mice using a Υδ T cell antibody. Results: Following OVA challenge, all mice exhibited mixed eosinophilic/neutrophilic airway inflammatory profiles and elevated serum OVA-IgE. Whereas OVA/alum sensitized mice had moderate inflammation and AHR, OVA/CFA sensitized mice had significantly greater inflammation but lacked AHR. This correlated with a shift in IL-17 production from CD4+ to Υδ T cells. Additionally, OVA/CFA sensitized mice, given a Υδ TCR stimulatory antibody, showed increased frequencies of IL-17-Υδ T cells and diminished airway reactivity and eosinophilia. Conclusions: Thus, the conditions of antigen sensitization influence the profile of cells that produce IL-17, the balance of which may then modulate the airway inflammatory responses, including AHR. The possibility for IL-17-Υδ T cells to reduce AHR and robust eosinophilic inflammation provides evidence that therapeutic approaches focused on stimulating and increasing airway IL-17-Υδ T cells may be an effective alternative in treating steroid resistant, severe asthma. [ABSTRACT FROM AUTHOR]