C3aR is expressed on certain parenchymal cells, including epithelial and endothelial cells, as well as on hematopoietic cells, including macrophages, dendritic cells, and eosinophils. During lung inflammation, C3a/C3aR mediated signaling in lung epithelial cells induces the expression of Muc5ac. In addition, C3a induces the expression of IL-8 from an epithelial cell line. Reports have also shown that C3a regulates helper T cell responses by modulating the function of antigen presenting cells. To further characterize the mechanism of C3a-mediated suppression of pulmonary Th17 responses, we sought to determine whether C3aR expression on hematopoietic or parenchymal cells is required to suppress the allergen-specific Th17 responses in the lung. Histologic examination and BAL fluid analysis Tulathromycin B showed that C3aR-deficient mice exhibited increased neutrophils in the airway, and that anti-IL-17 treatment specifically reduced the number of neutrophils in BAL fluid with little effects on airway reactivity and mucus production. Our results thus demonstrate that C3aR signaling on hematopoietic cells suppresses the generation of allergen-specific Th17 cells in the lung and neutrophilia in the airway via a Treg independent mechanism. Contribution of Th2 cells and their cytokines to allergic asthma has been well described. In addition, growing evidence has demonstrated the non-redundant role of Th17 cells and their cytokines in allergic lung inflammation. In particular, Th17 cells have been proposed to mediate neutrophilic lung inflammation as well as steroid resistant severe form of asthma. Moreover, the clinical severity of asthma is tightly associated with the amount of IL-17 in sputum and circulation in humans. Therefore it is likely that Th2 and Th17 responses mediate different forms of allergic lung inflammation, or are important regulators at different stages during lung inflammation. Our study provides experimental evidence that blockade of C3aR signal may Mepiroxol induce increased Th17 responses and neutrophilia in the airway. A recent study has attempted to 
use C3aR antagonist for the treatment of allergic lung inflammation in mice. However, based on the present study, the use of C3aR antagonist may induce neutrophilic lung inflammation, and thus more cautious consideration will be needed for the use of C3a/C3aR antagonist in clinical setting. In addition to its well-known functions in host defense, the role of the complement system in adaptive immunity is only in the past several years been fully appreciated. For instance, complement C5a has been shown to promote Th17-mediated autoimmune arthritis in SKG mice and experimental autoimmune encephalomyelitis by inducing IL-6 from antigen-presenting cells. On the other hand, it has been shown that C5aR-deficient DCs produce higher amounts of TGF-b and facilitate the generation of Th17 cells, indicating an inhibitory role of C5a on Th17 responses. More recently, C5a has also been reported to suppress the production IL-17 and IL-23 from macrophages in an animal model of septic shock by inducing IL-10. In addition, Lajoie et al have recently described the opposing role of C3a and C5a in regulating Th17 responses in an animal model of allergic asthma induced by house dust mite extract. They showed that C3a stimulates IL-23 production from dendritic cells, and that C3aRdeficient mice had fewer Th17 cells in the airway in their asthma model.