scholarly journals Prophylactic and Therapeutic Effects of Oral Immunotherapy on Birch Pollen-Induced Allergic Conjunctivitis in Mice with a Rice-Based Edible Vaccine Expressing a Hypoallergenic Birch Pollen Allergen

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3361
Author(s):  
Waka Ishida ◽  
Tatsuma Kishimoto ◽  
Fumio Takaiwa ◽  
Ken Fukuda

We investigated the prophylactic and therapeutic effects of the oral administration of transgenic rice seeds expressing a hypoallergenic Bet v 1 derivative of allergic birch pollen conjunctivitis in mice. Transgenic rice seed depositing a chimeric molecule called TPC7 (tree pollen chimera 7) created by DNA shuffling of Bet v 1 family sequences from birch, alder and hazel in protein bodies of endosperm was generated. BALB/c mice were sensitized to birch pollen in alum and challenged with pollen in eyedrops. They were fed TPC7 transgenic or non-transgenic (control) rice seeds for 14 d before sensitization (prophylactic protocol) or 17 d after sensitization (therapeutic protocol). The clinical score and number of conjunctival eosinophils were significantly lower in TPC7-fed mice than in the control mice based on both the prophylactic and therapeutic protocols. Serum concentration of allergen-specific IgE did not differ between TPC7-fed and control groups in either protocol. Prophylactic administration of TPC7 downregulated the production of IL-4 and IFN-γ, whereas therapeutic administration of TPC7 upregulated the production of IFN-γ by allergen-stimulated splenocytes. Prophylactic or therapeutic oral administration of transgenic rice expressing TPC7 suppressed birch pollen-induced allergic conjunctivitis in mice. Feeding transgenic rice is a potentially effective approach as an allergen-specific immunotherapy for allergic conjunctivitis.

2013 ◽  
Vol 54 (6) ◽  
pp. 917-933 ◽  
Author(s):  
Shuyi Wang ◽  
Hideyuki Takahashi ◽  
Hiroyuki Kajiura ◽  
Taiji Kawakatsu ◽  
Kazuhito Fujiyama ◽  
...  

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4409
Author(s):  
Jinjoo Kang ◽  
Soyoung Lee ◽  
Namkyung Kim ◽  
Hima Dhakal ◽  
Taeg-Kyu Kwon ◽  
...  

The extracts of Schisandra chinensis (Turcz.) Baill. (Schisandraceae) have various therapeutic effects, including inflammation and allergy. In this study, gomisin M2 (GM2) was isolated from S. chinensis and its beneficial effects were assessed against atopic dermatitis (AD). We evaluated the therapeutic effects of GM2 on 2,4-dinitrochlorobenzene (DNCB) and Dermatophagoides farinae extract (DFE)-induced AD-like skin lesions with BALB/c mice ears and within the tumor necrosis factor (TNF)-α and interferon (IFN)-γ-stimulated keratinocytes. The oral administration of GM2 resulted in reduced epidermal and dermal thickness, infiltration of tissue eosinophils, mast cells, and helper T cells in AD-like lesions. GM2 suppressed the expression of IL-1β, IL-4, IL-5, IL-6, IL-12a, and TSLP in ear tissue and the expression of IFN-γ, IL-4, and IL-17A in auricular lymph nodes. GM2 also inhibited STAT1 and NF-κB phosphorylation in DNCB/DFE-induced AD-like lesions. The oral administration of GM2 reduced levels of IgE (DFE-specific and total) and IgG2a in the mice sera, as well as protein levels of IL-4, IL-6, and TSLP in ear tissues. In TNF-α/IFN-γ-stimulated keratinocytes, GM2 significantly inhibited IL-1β, IL-6, CXCL8, and CCL22 through the suppression of STAT1 phosphorylation and the nuclear translocation of NF-κB. Taken together, these results indicate that GM2 is a biologically active compound that exhibits inhibitory effects on skin inflammation and suggests that GM2 might serve as a remedy in inflammatory skin diseases, specifically on AD.


2018 ◽  
Author(s):  
Fumio Takaiwa ◽  
Yuko Ogo ◽  
Yuhya Wakasa

AbstractApple food allergen Mal d 1 and birch pollen allergen Bet v 1 belong to the same pathogen related protein 10 (PR10) family. When each of these allergens was expressed as a secretory protein by fusion with the GFP reporter in transgenic rice by ligating an N terminal signal peptide and a C terminal KDEL ER retention signal under the control of the maize ubiquitin constitutive promoter, the GFP:Mald1 highly accumulated in various tissues, whereas the accumulation level of GFP:Betv1 was remarkably reduced in vegetative tissues except for seed. Analysis by RT-PCR exhibited that there was little difference in transcript levels between them, indicating the involvement of post-transcriptional regulation. To investigate the cause of such difference in accumulation levels, deletion analysis of the Mal d 1 and domain swapping between them were carried out in transgenic rice. These results showed that the region between positions 41-90 in the Mal d 1 is predominantly implicated in higher level accumulation in vegetative tissues as well as seed compared with the Bet v 1. It is notable that GFP:Mald1 directed by the ubiquitin promoter is deposited in huge PBs in aleurone layer rather than starchy endosperm.HighlightSpecific region of PR10 proteins is mainly implicated in their stability in vegetative tissues when expressed in transgenic rice.


2017 ◽  
Vol 27 (3) ◽  
pp. 457-465 ◽  
Author(s):  
Tomoya Hirota ◽  
Hiroto Tsuboi ◽  
Mana Iizuka-Koga ◽  
Hiroyuki Takahashi ◽  
Hiromitsu Asashima ◽  
...  

2016 ◽  
Vol 47 (5) ◽  
pp. 693-703 ◽  
Author(s):  
N. Groh ◽  
C. S. von Loetzen ◽  
B. Subbarayal ◽  
C. Möbs ◽  
L. Vogel ◽  
...  

2009 ◽  
Vol 29 (3) ◽  
pp. 183-192 ◽  
Author(s):  
Hanna Berkner ◽  
Philipp Neudecker ◽  
Diana Mittag ◽  
Barbara K. Ballmer-Weber ◽  
Kristian Schweimer ◽  
...  

In many cases, patients allergic to birch pollen also show allergic reactions after ingestion of certain fruits or vegetables. This observation is explained at the molecular level by cross-reactivity of IgE antibodies induced by sensitization to the major birch pollen allergen Bet v 1 with homologous food allergens. As IgE antibodies recognize conformational epitopes, a precise structural characterization of the allergens involved is necessary to understand cross-reactivity and thus to develop new methods of allergen-specific immunotherapy for allergic patients. Here, we report the three-dimensional solution structure of the soybean allergen Gly m 4, a member of the superfamily of Bet v 1 homologous proteins and a cross-reactant with IgE antibodies originally raised against Bet v 1 as shown by immunoblot inhibition and histamine release assays. Although the overall fold of Gly m 4 is very similar to that of Bet v 1, the three-dimensional structures of these proteins differ in detail. The Gly m 4 local structures that display those differences are also found in proteins from yellow lupine with known physiological function. The three-dimensional structure of Gly m 4 may thus shed some light on the physiological function of this subgroup of PR10 proteins (class 10 of pathogenesis-related proteins) and, in combination with immunological data, allow us to propose surface patches that might represent cross-reactive epitopes.


2014 ◽  
Vol 12 (8) ◽  
pp. 1143-1152 ◽  
Author(s):  
Mana Iizuka ◽  
Yuhya Wakasa ◽  
Hiroto Tsuboi ◽  
Hiromitsu Asashima ◽  
Tomoya Hirota ◽  
...  

2017 ◽  
Vol 40 (1) ◽  
pp. 28-34
Author(s):  
Tomoya HIROTA ◽  
Hiroto TSUBOI ◽  
Hiroyuki TAKAHASHI ◽  
Hiromitsu ASASHIMA ◽  
Masaru OHTA ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Oluwatoyin Akinfenwa ◽  
Huey-Jy Huang ◽  
Birgit Linhart ◽  
Margarete Focke-Tejkl ◽  
Susanne Vrtala ◽  
...  

IgE-mediated allergy to birch pollen affects more than 100 million patients world-wide. Bet v 1, a 17 kDa protein is the major allergen in birch pollen responsible for allergic rhinoconjunctivitis and asthma in birch pollen allergic patients. Allergen-specific immunotherapy (AIT) based on therapeutic administration of Bet v 1-containing vaccines is an effective treatment for birch pollen allergy but no allergen-specific forms of prevention are available. We developed a mouse model for IgE sensitization to Bet v 1 based on subcutaneous injection of aluminum-hydroxide adsorbed recombinant Bet v 1 and performed a detailed characterization of the specificities of the IgE, IgG and CD4+ T cell responses in sensitized mice using seven synthetic peptides of 31-42 amino acids length which comprised the Bet v 1 sequence and the epitopes recognized by human CD4+ T cells. We then d.emonstrate that preventive systemic administration of a mix of synthetic non-allergenic Bet v 1 peptides to 3-4 week old mice significantly reduced allergic immune responses, including IgE, IgG, IgE-mediated basophil activation, CD4+ T cell and IL-4 responses to the complete Bet v 1 allergen but not to the unrelated major grass pollen allergen Phl p 5, without inducing Bet v 1-specific allergic sensitization or adaptive immunity. Our results thus demonstrate that early preventive administration of non-allergenic synthetic T cell epitope-containing allergen peptides could be a safe strategy for the prevention of allergen-specific IgE sensitization.


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