CD30 ligand (CD30L) plays an important role in the amplification and/or activation of effector CD41 T cells, irrespective of Th cell subset. To examine the role of CD30L in allergic rhinitis, we evaluated an OVA model of allergic rhinitis in CD30L knock out (KO) mice on a BALB/c background sensitized with OVA. Symptoms of allergic rhinitis such as eosinophil infiltration into the nasal mucosa were drastically diminished in OVAsensitized CD30L KO mice following intranasal challenge with OVA. The levels of OVAspecific IgE in the sera and the Th2 response in nasopharynx-associated lymphoid tissues and cervical LNs of CD30L KO mice were significantly lower than those of WT mice following intranasal challenge with OVA. Intranasal administration of CD30-Ig during the effector phase with OVA significantly prevented the development of allergic rhinitis in WT mice. These results suggest that CD30L plays an important role in allergic rhinitis and that the inhibition of CD30L/CD30 signaling might be useful as a novel biological therapy for allergic rhinitis. during the allergic response, the induction phase and effector phase [17][18][19]. In the induction phase, Th2 cells and IgE specific for the allergen are generated in secondary lymphoid tissues. In the effector phase, allergic inflammation occurs in nasal mucosa and is further divided into two reactions: early-phase reaction and late-phase reaction. The early-phase reaction is characterized by sneezing, pruritus, nasal obstruction, and rhinorrhea, which are mediated by mast cells bound with IgE. The late-phase reaction is characterized with nasal congestion, inflammatory cells including basophils, eosinophils, mast cells, mononuclear cells, and neutrophils infiltration mediated by Th2 responses in mucosa and nasopharynx-associated lymphoid tissues (NALT) [20][21][22][23][24].In the present study, to investigate the effect of CD30/CD30L signal on the development of allergy rhinitis, the allergic rhinitis mouse model was investigated using CD30L KO mice. We showed that CD30L positively modulates the allergic symptoms and CD4 1 Th2 cell responses during the effector phase. Based on this result, the feasibility of CD30-Ig as an application in the treatment of allergic rhinitis has been confirmed. Implication of these findings for therapeutic application of CD30L/CD30 modulation for allergic rhinitis are discussed. Results CD30L KO mice showed impaired allergic inflammation in allergic rhinitisWe assessed the role of CD30L in a mice model of allergic rhinitis [25][26][27]. WT mice and CD30L KO mice were sensitized with OVA (25 mg) or PBS/aluminum hydroxide hydrate gel (alum) three times at 1-wk intervals, and then, from day 21 to day 35 after the first sensitization with OVA; mice were i.n. challenged with 20 mL of PBS or OVA (20 mg/mL) in the bilateral nostrils (Fig. 1A). Over a 5-min period after the last nasal drop of OVA or PBS, we counted the frequencies of sneeze and nasal rubbing of each mouse. The frequencies of nasal rubbing and sneezes after OVA challenge were si...

Sublingual immunotherapy (SLIT) has been considered to be a painless and efficacious therapeutic treatment of allergic rhinitis which is known as type I allergy of nasal mucosa. Nevertheless, its mechanisms need to be further investigated. In this study, we constructed an effective murine model of sublingual immunotherapy in allergic rhinitis, in which mice were sublingually administered with ovalbumin (OVA) followed by intraperitoneal sensitization and nasal challenge of OVA. Sublingually treated mice showed significantly decreased specific IgE responses as well as suppressed Th2 immune responses. Sublingual administration of OVA did not alter the frequency of CD4+CD25+ regulatory T cells (Tregs), but led to upregulation of Foxp3- and IL-10-specific mRNAs in the Tregs of cervical lymph nodes (CLN), which strongly suppressed Th2 cytokine production from CD4+CD25− effector T cells in vitro. Furthermore, sublingual administration of plasmids encoding the lymphoid chemokines CCL19 and CCL21-Ser DNA together with OVA suppressed allergic responses. These results suggest that IL-10-expressing CD4+CD25+Foxp3+ Tregs in CLN are involved in the suppression of allergic responses and that CCL19/CCL21 may contribute to it in mice that received SLIT.

These results suggest that oral administration of SKNS inhibits Th2 responses by enhancement of IL-12 release from macrophages via up-regulation of TLR4 expression.

OK-432, a preparation of a low-virulence strain (Su) of Streptococcus pyogenes (Group A) killed by a penicillin and lyophilized, is a stiff inducer of Th1 cytokines, and exerts anti-cancer effects in tumor-bearing mice. OK-432 has been reported to consist of many bacterial components, such as peptidoglycan, M-protein, etc. However, it is yet to be ascertained which bacterial component induces T helper 1 (Th1) responses. For the last decade, Toll-like receptor (TLR) family proteins are well elucidated to play a role in recognizing bacterial components and inducing interleukin (IL)-12 from macrophages. Above all, peptidoglycan seems to be the agonist of TLR2 rather than the obverse. In our present study, the role of TLR2 for the recognition of OK-432 by macrophages and the effects of OK-432 are examined on murine allergic rhinitis model. Interestingly, results show IL-12 production by macrophages derived from TLR2 knock-out (ko) mice was significantly decreased, in comparison with that of macrophages derived from wild-type mice. Moreover, in TLR2 ko mice, no regulatory effect of OK-432 was observed on an allergic rhinitis model. These data indicate that TLR2 signaling is involved in regulating OK-432-induced anti-T helper 2 (Th2) immunity, and may offer a new prophylactic and therapeutic approach using OK-432 to downregulate allergic disorders, such as allergic rhinitis.

Objective: Sublingual immunotherapy has been considered to be a painless and effective therapeutic treatment of patients with allergic rhinitis. Its mechanism of action has been elucidated, but there are still controversies among many reports between clinical efficacy and laboratory data. Therefore, its mechanism of action needs to be investigated further by using promising animal models such as rodents and monkeys. Materials and Methods: Bearing this in mind, in our present study, we successfully constructed an effective murine model for sublingual immunotherapy (SLIT) in allergic rhinitis in which mice were sublingually administered ovalbumin (OVA), followed by intraperitoneal (ip) sensitization and intranasal (i.n.) challenge of OVA. Results: To summarize our experimental data, nasal symptoms such as sneezing and nasal rubbing of sublingually treated mice were significantly attenuated in accordance with lower specific IgE antibodies in sera. Histological analysis of eosinophil recruitment in nasal mucosae reveals less allergic inflammation in sublingually treated mice. Interleukin-10 (IL-10) production and IL-10–specific mRNA gene expression of cultured submandibular lymph node (SMLN) cells with OVA, obtained from sublingually treated mice, were significantly higher than those of mice without sublingual treatment. Conclusion: These results demonstrate that sublingually introduced antigens can actually attenuate nasal symptoms in a murine allergic rhinitis model upon allergen exposures. Furthermore, our immunological data might indicate an important role of IL-10 producing T cells in SMLN to control nasal allergic reaction.