Epithelial

cells influence adaptive immunity by affecting the function of antigen presenting cells (APCs). Before the adaptive immune system can respond to inhaled allergens, the allergens have to be presented to them by professional selleckchem APCs such as macrophages, B cells, dendritic cells (DCs) or even by less professional APCs such as basophils and eosinophils [32, 33]. We have recently created TCR transgenic mice reactive to an immunogenic peptide of Der p 1, one of the major allergens of the HDM Dermatophagoides pteronyssinus, to address which APCs present inhaled allergens to naive CD4+ T cells in the draining mediastinal LNs of the lung [34]. Using this novel tool, only mucosal lining DCs were able to present HDM-derived antigens to T cells in the mediastinal nodes, whereas B cells or macrophages were unable to do so. These results are consistent with other reports demonstrating that only DCs, but not basophils, are able to induce Th2 immunity to HDM upon adoptive transfer

to naive mice, and that CD11chi cells (depleted via the CD11cDTR system) are necessary for the development of Th2 immunity to HDM allergens [8]. It is well established that DCs play a role both in the initiation and maintenance of allergic airway inflammation and asthma, and control many aspects of the disease, including BHR and GCM. DCs do so by controlling the recruitment and activation of Th2 cells, Fer-1 mouse by producing chemokines that attract eosinophils and Th2 cells, and by expressing co-stimulatory molecules for terminal Teff-cell generation (reviewed in [35]). The exact subtype of DCs exerting all these functions is a matter of intense study [36, 37]. In our hands, Th2 priming

was mainly performed by CD11b+ conventional (c)DCs, and not by CD103+ Meloxicam cDCs [34]. The restimulation of Th2 effector cells and recruitment of inflammatory cells was the function of CD11b+CD64+ FceRI+ monocyte-derived DCs [34]. In our previous work, we have found that plasmacytoid DCs induced anti-inflammatory effects and prevented asthma development, possibly by activating Treg cells [38, 39]. As epithelial cells represent the first line of defense to inhaled allergens and also express TLRs, they have the ability to sense the same stimuli as innate immune cells. Triggering of these epithelial cell pattern recognition receptors (PRRs) by PAMPs initiates NF-κB activation and leads to the release of pro-Th2 cytokines such as TSLP, granulocyte-macrophage colony stimulating factor (GM-CSF), IL-1α, IL-25, and IL-33 in mice [40-42]. These cytokines all share the capacity to activate DCs, which then coordinate the subsequent Th2-type immune response. DCs can, however, also be directly activated by stimulation of their PRRs. Additionally, PRR-dependent epithelial cell activation also results in the production of endogenous danger signals such as uric acid, adenosine triphosphate, and lysophosphatidic acid [43].