Asian Pacific journal of allergy and immunology · 2019
A novel allergen-specific therapy with regulatory T cells induced by CD40-silenced dendritic cells.
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Suzuki Motohiko, Yokota Makoto, Ozaki Shinya, Nakamura Yoshihisa
Аннотация
BACKGROUND: We previously reported that dendritic cells (DCs) transfected with CD40 siRNA and pulsed by ovalbumin (OVA) (CD40-silenced OVA DCs) inhibited allergic responses through facilitation of regulatory T cells (Tregs). However, to our knowledge, no prior study has examined allergen-specific therapy by administration of siRNA-induced Tregs for the control of allergy.
OBJECTIVE: We aimed to investigate the effect of Tregs induced in vitro on allergic responses and symptoms in vivo.
METHODS: Mice were treated with Tregs (OVA DCs-induced Tregs) induced by CD40-silenced OVA DCs or Tregs (nonantigen DCs-induced Tregs) induced by DCs transfected with CD40 siRNA and pulsed with no antigen, and the effects of these Tregs on allergic responses were estimated.
RESULTS: Administration of nonantigen DCs-induced Tregs prevented not only OVA-induced allergy but also keyhole limpet hemocyanin-induced allergy. Administration of OVA DCs-induced Tregs significantly reduced the number of sneezes and nasal rubbing movements, eosinophilia in the nasal mucosa, and the level of OVA-specific IgE in mice with OVA-induced allergy, compared with CD40-silenced nonantigen DC-induced Tregs in numbers 20 times greater, even in mice with established allergic rhinitis. Furthermore, Tregs induced by CD40-silneced DCs pulsed with Cry j 1, a major allergen of Japanese cedar pollen, inhibited Japanese cedar-induced allergy.
CONCLUSIONS: This study shows for the first time that both antigen-independent Tregs and antigen-specific Tregs can be induced by siRNA, and that therapy with siRNA-induced Tregs inhibits allergic responses and symptoms. It also shows that antigen-specific Tregs have more potent effects in inhibiting allergic responses than antigen-nonspecific Tregs.
OBJECTIVE: We aimed to investigate the effect of Tregs induced in vitro on allergic responses and symptoms in vivo.
METHODS: Mice were treated with Tregs (OVA DCs-induced Tregs) induced by CD40-silenced OVA DCs or Tregs (nonantigen DCs-induced Tregs) induced by DCs transfected with CD40 siRNA and pulsed with no antigen, and the effects of these Tregs on allergic responses were estimated.
RESULTS: Administration of nonantigen DCs-induced Tregs prevented not only OVA-induced allergy but also keyhole limpet hemocyanin-induced allergy. Administration of OVA DCs-induced Tregs significantly reduced the number of sneezes and nasal rubbing movements, eosinophilia in the nasal mucosa, and the level of OVA-specific IgE in mice with OVA-induced allergy, compared with CD40-silenced nonantigen DC-induced Tregs in numbers 20 times greater, even in mice with established allergic rhinitis. Furthermore, Tregs induced by CD40-silneced DCs pulsed with Cry j 1, a major allergen of Japanese cedar pollen, inhibited Japanese cedar-induced allergy.
CONCLUSIONS: This study shows for the first time that both antigen-independent Tregs and antigen-specific Tregs can be induced by siRNA, and that therapy with siRNA-induced Tregs inhibits allergic responses and symptoms. It also shows that antigen-specific Tregs have more potent effects in inhibiting allergic responses than antigen-nonspecific Tregs.