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

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Abstract

Objective

At least 3 years of sublingual immunotherapy (SLIT) is required to achieve long-term clinical tolerance for allergens. However, immunological changes with more than 3 years of SLIT have not yet been elucidated in detail. The present study investigated whether the numbers of regulatory T (Treg) cells and regulatory B (Breg) cells increased with 4 years of SLIT and if these increases correlated with clinical effects for pollinosis.

Methods

Seven Japanese cedar pollinosis patients received SLIT in 2014 or 2015 and continued treatment until May 2019. In May 2017 and May 2019, peripheral blood mononuclear cells (PBMCs) were collected from the patients, and analyzed by flow cytometer.

Results

(1) The visual analogue scale (VAS) was significantly higher in 2019 than in 2017. (2) The percentages of Foxp3+ Treg cells, type 1 regulatory T (Tr1) cells, and Breg cells in PBMCs were significantly higher in 2019 than in 2017. (3) The percentage of Foxp3+ Treg cells in PBMCs positively correlated with VAS, whereas those of Tr1 cells and Breg cells did not.

Conclusions

These results suggest that 4 years of SLIT is needed to achieve sustained increases in Foxp3+ Treg cells, which are closely associated with the efficacy of SLIT.

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Acknowledgements

The present study was supported by research funding from JSPS KAKENHI grant number 17K11370 (to Tetsuya Terada and Takeshi Nabe) and Setsunan University (to Masaya Matsuda, Kazuyuki Kitatani and Takeshi Nabe). The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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Author notes

  1. Tetsuya Terada and Masaya Matsuda contributed equally to this work.

Authors and Affiliations

  1. Department of Otolaryngology, Head and Neck Surgery, Osaka Medical College, Takatsuki, Osaka, Japan

    Tetsuya Terada, Yusuke Kikuoka, Yuko Inaka & Ryo Kawata

  2. Laboratory of Immunopharmacology, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka, Japan

    Masaya Matsuda, Miki Inaba, Junpei Hamaguchi, Naoki Takemoto, Harumi Sakae, Kennosuke Hashimoto, Hayato Shimora, Kazuyuki Kitatani & Takeshi Nabe

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  1. Tetsuya Terada
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Contributions

Tetsuya Terada, Masaya Matsuda, Kazuyuki Kitatani, Ryo Kawata, and Takeshi Nabe were involved in the study design, data collection, data interpretation, data analysis, and writing the manuscript. Miki Inaba, Junpei Hamaguchi, Naoki Takemoto, Harumi Sakae, Kennosuke Hashimoto and Hayato Shimora were involved in data collection, data interpretation, and data analysis. Yusuke Kikuoka and Yuko Inaka were involved in data collection. Takeshi Nabe has full access to the data, and is responsible for the integrity of data and final decision to submit this manuscript. All authors have approved the final version of this manuscript for submission.

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Correspondence to Takeshi Nabe.

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Terada, T., Matsuda, M., Inaba, M. et al. Sublingual immunotherapy for 4 years increased the number of Foxp3+ Treg cells, which correlated with clinical effects. Inflamm. Res. 70, 581–589 (2021). https://doi.org/10.1007/s00011-021-01460-3

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  • DOI: https://doi.org/10.1007/s00011-021-01460-3

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