Impacts of CD40- and CD86-Silenced Antigen-Specific B Cells on the Control of Allergies

2019 ◽  
Vol 33 (5) ◽  
pp. 513-523
Author(s):  
Motohiko Suzuki ◽  
Tamami Matsumoto ◽  
Kiichi Toyoda ◽  
Yoshihisa Nakamura ◽  
Shingo Murakami

Background We previously reported that CD40-silenced B cells inhibited allergic responses and symptoms. However, more potent therapies are needed. To our knowledge, the effects of CD86-silenced B cells and synergic effects of gene silencing in B cells by 2 small interfering RNAs (siRNAs) on allergic disease control have not been reported. Objective To investigate the effects of CD86-silenced B cells and synergic effects of gene silencing in B cells on allergic responses and symptoms. Methods Mice were treated with CD40- and/or CD86-silenced B cells transfected with siRNAs and pulsed with ovalbumin (OVA). And the effects of these B cells were estimated. Results CD86-silenced OVA-pulsed B cells significantly inhibited OVA-induced allergies. Treatment with CD40-/CD86-silenced OVA-pulsed B cells led to a significantly fewer sneezes and nasal rubbing movements, as well as lower OVA-specific immunoglobulin E (IgE) levels, than that with CD40-silenced or CD86-silenced OVA-pulsed B cells alone. These inhibitory effects were observed prior to sensitization as well as after the establishment of allergic rhinitis. CD40-/CD86-silenced OVA-pulsed B cells did not inhibit keyhole limpet hemocyanin-induced allergies. CD40-/CD86-silenced OVA-pulsed B cells also significantly inhibited allergic symptoms and OVA-specific IgE level in sera compared with CD40-/CD86-silenced OVA-pulsed dendritic cells (DCs). In addition, CD19+CD40− B cells significantly increased in the nasal tissue after intravenous administration of these cells. Furthermore, CD40-/CD86-silenced B cells inhibited allergic symptoms caused by Cry j 1, a major aeroallergen of Japanese cedar pollen, and Cry j 1-specific IgE in sera. Conclusion This study showed, for the first time, that siRNA-induced CD86-silenced B cells significantly inhibited allergic responses and symptoms antigen-specifically, and that siRNA-induced CD40-/CD86-silenced antigen-specific B cells are a more useful antigen-specific therapy than CD40- or CD86-silenced B cells alone for the control of allergies. Furthermore, it was shown that CD40-/CD86-silenced B cells have stronger inhibition of IgE production and allergic symptoms than CD40-/CD86-silenced DCs.

Aerobiologia ◽  
1998 ◽  
Vol 14 (4) ◽  
pp. 321-324 ◽  
Author(s):  
Kensei Naito ◽  
G. Ishii ◽  
T. Ogawa ◽  
N. Yokoyama ◽  
S. Iwata

2021 ◽  
Vol 70 (1) ◽  
pp. 105-113
Author(s):  
Takashi Kanno ◽  
Yoshiyuki Adachi ◽  
Katsuyo Ohashi-Doi ◽  
Hiroki Matsuhara ◽  
Rie Hiratsuka ◽  
...  

2014 ◽  
Vol 63 (3) ◽  
pp. 467-473 ◽  
Author(s):  
Hiroshi Sakaida ◽  
Sawako Masuda ◽  
Kazuhiko Takeuchi

Science ◽  
2019 ◽  
Vol 365 (6456) ◽  
pp. eaaw6433 ◽  
Author(s):  
Uthaman Gowthaman ◽  
Jennifer S. Chen ◽  
Biyan Zhang ◽  
William F. Flynn ◽  
Yisi Lu ◽  
...  

Cross-linking of high-affinity immunoglobulin E (IgE) results in the life-threatening allergic reaction anaphylaxis. Yet the cellular mechanisms that induce B cells to produce IgE in response to allergens remain poorly understood. T follicular helper (TFH) cells direct the affinity and isotype of antibodies produced by B cells. Although TFH cell–derived interleukin-4 (IL-4) is necessary for IgE production, it is not sufficient. We report a rare population of IL-13–producing TFH cells present in mice and humans with IgE to allergens, but not when allergen-specific IgE was absent or only low-affinity. These “TFH13” cells have an unusual cytokine profile (IL-13hiIL-4hiIL-5hiIL-21lo) and coexpress the transcription factors BCL6 and GATA3. TFH13 cells are required for production of high- but not low-affinity IgE and subsequent allergen-induced anaphylaxis. Blocking TFH13 cells may represent an alternative therapeutic target to ameliorate anaphylaxis.


2018 ◽  
Vol 5 (3) ◽  
pp. 79 ◽  
Author(s):  
Takashi Kuribayashi ◽  
Davide Cossu ◽  
Eiichi Momotani

Levels of Japanese cedar pollen (Cryptomeria japonica) have increased in Japan and cedar pollinosis caused by Japanese cedar pollen has been reported in dogs. Serum levels of immunoglobulin E (IgE) against Cry j 1 and Cry j 2 in dogs raised in institutes and treated at veterinary hospitals in Japan were thus investigated. A total of 71 sera obtained from two institutes and 87 sera obtained from veterinary hospitals in the Hyogo and Kanagawa Prefectures were analyzed in this study. Serum levels of IgE were measured using the enzyme-linked immunosorbent assay with commercial purified Cry j 1 and Cry j 2. IgE against Cry j 1 and Cry j 2 in sera obtained from the two institutes were detected, despite the dogs being bred in enclosed areas. Moreover, significant differences were noted in the serum levels of IgE against Cry j 1 and Cry j 2 between the two institutes. The number of samples showing Cry j 1 or Cry j 2 levels above the cut-off values was greater in the Kanagawa Prefecture than in the Hyogo Prefecture. In total, 14 dogs showed Cry j 1 and Cry j 2 levels greater than the cut-off values in the Hyogo Prefecture, and only three such dogs were seen in the Kanagawa Prefecture. A significant correlation between serum levels against both allergens was observed (r2 = 0.6931, p < 0.0001).


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