Untitled

Hashiguchi, Masaaki; Hachimura, Satoshi; Ametani, Akio; Kaminogawa, Shuichi

doi:10.1023/a:1008102304740

Cited by 6 publications

(4 citation statements)

References 26 publications

(23 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our study, we demonstrated that the low IAV infection dose tended to result in a sufficient Th1 immune response to clear the viral infection and we observed a trend towards a Th2 immune response after a high dose of infection. These results are consistent with data from previous studies, which have already shown that low-dose infection or low antigen concentration favors the induction of Th1 responses, whereas high-dose infection preferentially induces Th2 responses ( 51 – 53 ). Our findings are consistent with data from a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) study in which COVID-19 patients exhibited an overly reactive Th2 response to the virus ( 54 ).…”

Section: Discussionsupporting

confidence: 93%

MEK-inhibitor treatment reduces the induction of regulatory T cells in mice after influenza A virus infection

Koch-Heier,

Vogel,

Füll

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

Regulatory T cells (Tregs) play a crucial and complex role in balancing the immune response to viral infection. Primarily, they serve to regulate the immune response by limiting the expression of proinflammatory cytokines, reducing inflammation in infected tissue, and limiting virus-specific T cell responses. But excessive activity of Tregs can also be detrimental and hinder the ability to effectively clear viral infection, leading to prolonged disease and potential worsening of disease severity. Not much is known about the impact of Tregs during severe influenza. In the present study, we show that CD4+/CD25+FoxP3+ Tregs are strongly involved in disease progression during influenza A virus (IAV) infection in mice. By comparing sublethal with lethal dose infection in vivo, we found that not the viral load but an increased number of CD4+/CD25+FoxP3+ Tregs may impair the immune response by suppressing virus specific CD8+ T cells and favors disease progression. Moreover, the transfer of induced Tregs into mice with mild disease symptoms had a negative and prolonged effect on disease outcome, emphasizing their importance for pathogenesis. Furthermore, treatment with MEK-inhibitors resulted in a significant reduction of induced Tregs in vitro and in vivo and positively influenced the progression of the disease. Our results demonstrate that CD4+/CD25+FoxP3+ Tregs are involved in the pathogenesis of severe influenza and indicate the potential of the MEK-inhibitor zapnometinib to modulate CD4+/CD25+FoxP3+ Tregs. Thus, making MEK-inhibitors even more promising for the treatment of severe influenza virus infections.

show abstract

Section: Discussionsupporting

confidence: 93%

MEK-inhibitor treatment reduces the induction of regulatory T cells in mice after influenza A virus infection

Koch-Heier,

Vogel,

Füll

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…High-dose antigen exposure can enhance Th2 polarization [37,38,39] and does not favor the induction of Foxp3+ T reg cells [40]. This hypothesis is supported in our study as the high-dosage AIT group had minimal Foxp3+ cells in the gut while the overexpression of Th2 cytokines was prominent.…”

Section: Discussionsupporting

confidence: 80%

Low-Dose Allergen-Specific Immunotherapy Induces Tolerance in a Murine Model of Shrimp Allergy

Leung

Wai

Shu

et al. 2017

Int Arch Allergy Immunol

View full text Add to dashboard Cite

Background: The efficacy and safety of allergen-specific immunotherapy (AIT) are highly dose-dependent. Methods: We investigated the dosage effects of AIT and the underlying mechanisms in a murine model of shrimp hypersensitivity. BALB/c mice were sensitized with recombinant shrimp allergen rMet e 1 and challenged orally with a high dose of rMet e 1 to elicit an allergic response. These sensitized mice were then treated with a low (0.01 mg), medium (0.05 mg), or high dosage (0.1 mg) of rMet e 1 intraperitoneally before receiving a second oral challenge. The allergic responses and immunological changes in the gut were compared between animals receiving different dosages. Results: We found that all sensitized mice that received rMet e 1 immunotherapy were desensitized, regardless of the dosage, and protected at the second oral challenge. Nevertheless, the mice in the high-dosage group experienced severe systemic reactions during the treatment phase. In contrast, regulatory T (T_reg) cell-associated genes were upregulated only in the low- and medium-dosage groups, and Foxp3+ cells were more abundant in the gut lymphoid tissues than in the high-dosage group. Conclusions: Our results demonstrate that low-dosage immunotherapy favors the induction of local Foxp3+ T_reg cells and the upregulation of regulatory cytokines. The safety advantages and long-term efficacy of low-dosage immunotherapy should be taken into consideration when developing immunotherapy dose schedules.

show abstract

“…This dose-dependent effect has been observed in 2 trials of intranasal AIT for rhinitis and rhinoconjunctivitis 35 , 36 and in a study of AIT in a murine model of shrimp allergy 33 . This lower effect may be explained by the results of previous studies showing that a high concentration of antigen exposure is related with a Th2 polarization and a lack of FoxP3 + Treg induction 37 , 38 …”

Section: Discussionmentioning

confidence: 97%

Glycosylated nanostructures in sublingual immunotherapy induce long-lasting tolerance in LTP allergy mouse model

Rodríguez

Ramos‐Soriano

Perkins

et al. 2019

Sci Rep

View full text Add to dashboard Cite

An effective specific immunotherapy should contain elements to generate specific recognition (T-cell peptides) and to modulate the immunological response towards a Th1/Treg pattern by enhancing dendritic cells (DCs). We propose a novel sublingual immunotherapy for peach allergy, using systems, that combine Prup3-T-cell peptides with mannose dendrons (D1ManPrup3 and D4ManPrup3). Peach anaphylactic mice were treated 1, 2 and 5 nM concentrations. Tolerance was assessed one/five weeks after finishing treatment by determining in vivo/in vitro parameters after challenge with Prup3. Only mice receiving D1ManPrup3 at 2 nM were protected from anaphylaxis (no temperature changes, decrease in Prup3-sIgE and -sIgG1 antibody levels, and secreting cells) compared to PBS-treated mice. Moreover, an increase of Treg-cells and regulatory cytokines (IL-10+/IFN-γ+) in CD4+-T-cells and DCs were found. These changes were maintained at least five weeks after stopping treatment. D1ManPrup3 is an effective new approach of immunotherapy inducing protection from anaphylaxis which persists after finishing treatment.

show abstract

Untitled

Cited by 6 publications

References 26 publications

MEK-inhibitor treatment reduces the induction of regulatory T cells in mice after influenza A virus infection

MEK-inhibitor treatment reduces the induction of regulatory T cells in mice after influenza A virus infection

Low-Dose Allergen-Specific Immunotherapy Induces Tolerance in a Murine Model of Shrimp Allergy

Glycosylated nanostructures in sublingual immunotherapy induce long-lasting tolerance in LTP allergy mouse model

Contact Info

Product

Resources

About