Lung Expansion of Th1, Th2, Th17 and Tregs Figure 10. Chemokines related to Th1, Th2, Th17 and Treg cells during allergic inflammation. A) Fold change of genes related to chemoattractants to Th1, Th2, Th17 and Treg cells in peribronchial, perivascular and alveolar tissue. Fold change is calculated by comparing OVA exposed mice to PBS control. 3 fold change threshold indicated by dotted line was considered biological relevant. B) Network of differentially expressed genes in OVA exposed mice compared to PBS exposed controls. A network of chemokines, generated by Ingenuity Pathways Analysis (3.0 fold change threshold), of OVA/OVA mice compared to OVA/PBS mice. The expression of these genes in three lung microenvironments was examined; peribronchial, perivascular and alveolar tissue. Lines indicate relationships between molecules (dashed line = indirect interaction). Arrows at the end of these lines indicate the direction of the interaction. Molecules that are up-regulated and down-regulated in the dataset are coloured red and green respectively. Darker colouring of the molecules indicates a higher fold change. Grey molecules did not meet the threshold of 3 fold change. Uncoloured molecules have been added from the Ingenuity Knowledge Base. The exact fold change values of each molecule are shown in Table 1. doi:10.1371/journal.pone.0019889.g010 During the past two decades, the Th1/Th2 paradigm of a balance to regulate development of allergy has prevailed, and these two cell types have been implicated in the pathogenesis of different inflammatory diseases including asthma. However, recent evidence suggests that the dichotomous view of Th-cells differentiation must be broadened to several other T-cells. In fact, IL-17-producing Th17 cells appear to play a critical role in autoimmunity and neutrophilic inflammation [24]. Furthermore, anti-inflammatory processes have been suggested to involve Treg cells that suppress the functional activity of other effector T-cells [25–27]. However, their relative presence in lung tissue in allergic inflammation has not previously been described. The current study is thus the first to document the changes in Th1, Th2, and Th17 and Treg cells in the lung during allergic airway inflammation. Interestingly, all cells increase in number, but most prominently the Th2 cells, support their major functional role in allergic inflammation. Even though a relative reduction of Foxp3 cells in the CD4+CD25+ fraction was observed after allergen exposure, it should be noted that the total number of Foxp3 cells indeed are increased. Importantly, in the CD4+CD252 fraction, the Foxp3+ cells are increased both as total and relative numbers. It has been argued that attenuation of Foxp3 can cause Treg to revert back to effector T cells, for example Th2-like cells, arguing for plasticity in this population [28,29]. In the case of Th1 and Th17 cell populations, both of these change in similar patterns during allergen exposure. One interesting finding is that the relative expression of the studied transcription factors is quite small in the PLoS ONE | www.plosone.org 14 May 2011 | Volume 6 | Issue 5 | e19889