Sublingual immunotherapy for 4 years increased the number of Foxp3+ Treg cells, which correlated with clinical effects

Takato, Tsuyoshi; Matsuda, Masaya; Inaba, Miki; Hamaguchi, Junpei; Takemoto, Naoki; Kikuoka, Yusuke; Inaka, Yuko; Sakae, Harumi; Hashimoto, Kennosuke; Shimora, Hayato; Kitatani, Kazuyuki; Kawata, Ryo; Nabe, Takeshi

doi:10.1007/s00011-021-01460-3

Cited by 13 publications

(17 citation statements)

References 33 publications

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“…In general, AITs may have an unfavorable effect on RADs because of their mechanism. Although not fully understood, it is mainly due to the suppression of the Th2-type immune response by Treg induction [ 28 ], allergen-specific immune deviation from Th2 to Th1 represented by interferon-γ (IFN-γ) production [ 29 , 30 ], and antigen-specific IgG4 antibody production [ 31 ]. Of these, Th1-type cytokines, such as IFN-γ, have been reported to contribute to the pathogenesis of RADs.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness and safety of allergen immunotherapy in patients with allergic rhinitis complicated by rheumatic autoimmune diseases: a case series study

Fujioka

Kasahara

Kida

et al. 2022

Allergy Asthma Clin Immunol

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Background Allergen immunotherapy (AIT) is the only treatment that has modified the natural history of allergic diseases. However, since its overall effect on the immune system has not been elucidated, AIT is either absolutely or relatively contraindicated in patients with rheumatic autoimmune diseases (RADs). Therefore, there have been no long-term observations of patients with RADs receiving AIT; thus, the effectiveness and safety of AIT in these patients remain unclear. Methods This was a single-center retrospective observational study. RAD patients receiving AIT for allergic rhinitis at our institution were selected. Changes in the activity of RAD patients were investigated for 2 years from baseline, including those who discontinued AIT. The effectiveness of AIT was also investigated using the Japan Allergic Rhinitis Standard Quality of Life Questionnaire. Results Thirteen patients with RADs were enrolled in the study. All patients received sublingual immunotherapy, of which four discontinued AIT owing to adverse events. Among all patients, the symptoms of RADs in three patients worsened during the observation period; however, none of them were causally related to AIT. Most of the adverse events associated with AIT were mild, in which only one patient required drug intervention due to worsening rhinitis symptoms. In the nine patients who were able to continue AIT, their eye and nasal symptom scores showed a significant improvement from 1.67 (1.5–2.0) at baseline to 0.67 (0–1.17) in the 2nd year of treatment (p = 0.0141). Conclusions AIT is a safe and effective treatment modality for patients with allergic rhinitis complicated by RADs.

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Section: Discussionmentioning

confidence: 99%

Effectiveness and safety of allergen immunotherapy in patients with allergic rhinitis complicated by rheumatic autoimmune diseases: a case series study

Fujioka

Kasahara

Kida

et al. 2022

Allergy Asthma Clin Immunol

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“…On the other hand, our group ( 82 ) reported that both numbers of Tr1 cells and Foxp3 + Treg cells were markedly increased in the peripheral blood of Japanese cedar pollinosis patients who had received SLIT. Moreover, the number of Foxp3 + Treg cells positively correlated with improvement in nasal symptoms, whereas those of Tr1 cells did not ( 82 ). Therefore, Foxp3 + Treg cells rather than Tr1 cells may have contributed to the clinical effects of SLIT.…”

Section: Clinical Relevance Of Tr1 Cells In Allergy and Aitmentioning

confidence: 98%

“…This result suggested that AITs may be effective for allergic diseases because of the conversion of allergen-specific effector Th2 cells into tolerance-inducing Tr1 cells by repeated allergen administrations. Indeed, many studies [reviewed in ( 10 , 87 )] have demonstrated that AIT can be effective for various allergic diseases, and the frequency of allergen-specific Tr1 cells was correlated with the decrease in clinical scores ( 79 – 82 ). Taken together, these studies suggested that Tr1 cells play a critical role in the induction of immunotolerance to allergens in humans.…”

Section: Clinical Relevance Of Tr1 Cells In Allergy and Aitmentioning

confidence: 99%

“…These data imply that the increase in Tr1 cells but not Foxp3 + Treg cells could be crucial for the induction of immunotolerance to allergens by SCIT. On the other hand, our group ( 82 ) reported that both numbers of Tr1 cells and Foxp3 + Treg cells were markedly increased in the peripheral blood of Japanese cedar pollinosis patients who had received SLIT. Moreover, the number of Foxp3 + Treg cells positively correlated with improvement in nasal symptoms, whereas those of Tr1 cells did not ( 82 ).…”

Section: Clinical Relevance Of Tr1 Cells In Allergy and Aitmentioning

confidence: 99%

“…Although there is a lack of specific markers of Tr1 cells, the existence of various allergen-specific Tr1 cells whose characteristic features are Foxp3-negative IL-10-producing CD4 + T cells, have also been reported in allergic models of mice ( 68 – 70 ) and allergic patients ( 71 – 78 ). Several clinical studies ( 79 – 82 ) demonstrated that the number of Tr1 cells increased in AIT-treated allergic patients, and the number such cells correlated with the clinical score. These studies suggested that Tr1 cells have crucial roles in immune tolerance to allergens.…”

Section: Introductionmentioning

confidence: 95%

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Roles of type 1 regulatory T (Tr1) cells in allergen-specific immunotherapy

et al. 2022

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Allergen-specific immunotherapy (AIT) is the only causative treatment for allergic diseases by modification of the immune response to allergens. A key feature of AIT is to induce immunotolerance to allergens by generating antigen-specific regulatory T (Treg) cells in allergic patients. Type 1 regulatory T (Tr1) cells and forkhead box protein 3 (Foxp3)-expressing Treg cells are well known among Treg cell subsets. Foxp3 was identified as a master transcription factor of Treg cells, and its expression is necessary for their suppressive activity. In contrast to Foxp3+ Treg cells, the master transcription factor of Tr1 cells has not been elucidated. Nevertheless, Tr1 cells are generally considered as a distinct subset of Treg cells induced in the periphery during antigen exposure in tolerogenic conditions and can produce large amounts of anti-inflammatory cytokines such as interleukin-10 and transforming growth factor-β, followed by down-regulation of the function of effector immune cells independently of Foxp3 expression. Since the discovery of Tr1 cells more than 20 years ago, research on Tr1 cells has expanded our understanding of the mechanism of AIT. Although the direct precursors and true identity of these cells continues to be disputed, we and others have demonstrated that Tr1 cells are induced in the periphery by AIT, and the induced cells are re-activated by antigens, followed by suppression of allergic symptoms. In this review, we discuss the immune mechanisms for the induction of Tr1 cells by AIT and the immune-suppressive roles of Tr1 cells in AIT.

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Allergen immunotherapy in asthma

Nakagome,

Nagata

2024

Allergology International

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Sublingual immunotherapy for 4 years increased the number of Foxp3+ Treg cells, which correlated with clinical effects

Cited by 13 publications

References 33 publications

Effectiveness and safety of allergen immunotherapy in patients with allergic rhinitis complicated by rheumatic autoimmune diseases: a case series study

Effectiveness and safety of allergen immunotherapy in patients with allergic rhinitis complicated by rheumatic autoimmune diseases: a case series study

Roles of type 1 regulatory T (Tr1) cells in allergen-specific immunotherapy

Allergen immunotherapy in asthma

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