Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Oct;150(4):850-860.e5.
doi: 10.1016/j.jaci.2022.06.024. Epub 2022 Jul 19.

Single-cell immunoprofiling after immunotherapy for allergic rhinitis reveals functional suppression of pathogenic TH2 cells and clonal conversion

Tomohisa Iinuma  1 , Masahiro Kiuchi  2 , Kiyoshi Hirahara  2 , Junya Kurita  1 , Kota Kokubo  2 , Hiroyuki Yagyu  2 , Riyo Yoneda  1 , Tomoyuki Arai  1 , Yuri Sonobe  2 , Masaki Fukuyo  3 , Atsushi Kaneda  3 , Syuji Yonekura  1 , Toshinori Nakayama  4 , Yoshitaka Okamoto  5 , Toyoyuki Hanazawa  6
Affiliations
Free article

Single-cell immunoprofiling after immunotherapy for allergic rhinitis reveals functional suppression of pathogenic TH2 cells and clonal conversion

Tomohisa Iinuma et al. J Allergy Clin Immunol. 2022 Oct.
Free article

Abstract

Background: Allergic rhinitis is a growing problem worldwide. Currently the only treatment that can modify the disease is antigen-specific immunotherapy, but its mechanism of action is not fully understood.

Objective: We comprehensively investigated the role and changes of antigen-specific T cells before and after sublingual immunotherapy (SLIT) for Japanese cedar pollinosis.

Methods: We cultured peripheral blood mononuclear cells obtained both before and 1 year after initiating SLIT and used a combination of single-cell RNA sequencing and repertoire sequencing. To investigate biomarkers, we used cells from patients participating a phase 2/3 trial of SLIT tablets for Japanese cedar pollinosis and cells from outpatients with good and poor response.

Results: Antigen-stimulated culturing after SLIT led to clonal expansion of TH2 and regulatory T cells, and most of these CD4+ T cells retained their CDR3 regions before and after treatment, indicating antigen-specific clonal responses and differentiation resulting from SLIT. However, SLIT reduced the number of clonal functional TH2 cells but increased the trans-type TH2 cell population that expresses musculin (MSC), TGF-β, and IL-2. Trajectory analysis suggested that SLIT induced clonal differentiation of the trans-type TH2 cells differentiated into regulatory T cells. Using real-time PCR, we found that the MSC levels increased in the active SLIT group and those with good response after 1 year of treatment.

Conclusion: The combination of single-cell RNA sequencing and repertoire analysis helped reveal part of the underlying mechanism: SLIT promotes the expression of MSC on pathogenic TH2 cells and suppresses their function. MSC may be a potential biomarker of SLIT for allergic rhinitis.

Keywords: Allergic rhinitis; Japanese cedar pollinosis; T cell; musculin; repertoire sequencing; single-cell RNA sequencing; sublingual immunotherapy.

PubMed Disclaimer

Publication types