Single-cell immunoprofiling after immunotherapy for allergic rhinitis reveals functional suppression of pathogenic T(H)2 cells and clonal conversion

Iinuma T, Kiuchi M, Hirahara K, Kurita J, Kokubo K, Yagyu H, Yoneda R, Arai T, Sonobe Y, Fukuyo M, Kaneda A, Yonekura S, Nakayama T, Okamoto Y, Hanazawa T. J Allergy Clin Immunol. 2022 Oct;150(4):850-860.e5. doi: 10.1016/j.jaci.2022.06.024.

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 T(H)2 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 T(H)2 cells but increased the trans-type T(H)2 cell population that expresses musculin (MSC), TGF-beta, and IL-2. Trajectory analysis suggested that SLIT induced clonal differentiation of the trans-type T(H)2 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 T(H)2 cells and suppresses their function. MSC may be a potential biomarker of SLIT for allergic rhinitis.

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