935,** P < 0.01) and the Treg transcription factor FOXP3 (r4 = 0.683, ** P < 0.01), respectively (Fig. 5). However, no correlation was found between eosinophil numbers and the Th1 transcription factor T-bet (r3 = 0.084, Alpelisib clinical trial P > 0.05; Fig. 5). Lactoferrin may be a potential therapeutic for the prevention and treatment of AR due to its immune-modulating properties. In this study, we demonstrated that LF treatment reduced inflammatory responses and helped alleviate symptoms of AR in mice. LF treatment had a better anti-inflammatory effect prior to OVA challenge than after OVA challenge. The anti-inflammatory effects included lower levels of eosinophils, goblet cells,
IL-5, IL-17, GATA-3 and ROR-C in mice pretreated with LF. Thus, LF may influence immune cell function and inhibit pro-inflammatory responses
to antigen exposure. Lactoferrin can regulate immune cell function by cross-linking LF-specific receptors present on many different immune cell populations, including activated lymphocytes and eosinophils. LF has two kinds of receptors such as high- and low-affinity receptors. The former are localized only at the surfaces of activated lymphocytes, while the latter are characterized on monocytes, eosinophils and neutrophils, which are immunologically different from the former [23]. Moreover, LF receptors of T cells are also localized Erlotinib in the peri-membrane area inside the cells and interference with transmission of intracellular signals [24, 25]. Our present results dipyridamole showed that LF had a better anti-inflammatory effect for mice receiving it before OVA challenge than those receiving it after OVA challenge. These differences may have a close relationship with both LF receptors expression on T cell surfaces and their binding status. LF receptors are expressed only by activated T cells, but not static T cells [25]. When OVA challenge starts after rhLF administration, it is likely that LF causes T cell receptor cross-linking, which
leads to the inhibition of T cell activation, reduces the releasing of inflammatory factors such as IL-5 and IL-17 and further alleviates the degree of inflammation. However, When LF is administered after OVA challenge, T cells, such as Th2 and Th17 cells, are already activated and have initiated an inflammatory cascade, while rhLF has no inhibitory effects on such inflammatory mediators as have been released out by activated T cells. LF receptors are also expressed on respiratory epithelial cells [26]. It is possible that rhLF regulates nasal local immunity through the LF receptors on both the activated local lymphocytes and airway epithelial cells in the nasal mucosa. However, this must be confirmed by an examination of the expression of LF receptors. The development of AR is associated with the expansion of pathogen- and allergen-experienced effector T cells and an imbalance in Th1 and Th2 cell responses with a shift towards a Th2 phenotype.