論文

査読有り 国際誌
2022年5月11日

Distinct disease-specific Tfh cell populations in two different fibrotic diseases: IgG4-related disease and Kimura's disease.

The Journal of allergy and clinical immunology
  • Ryusuke Munemura
  • Takashi Maehara
  • Yuka Murakami
  • Risako Koga
  • Ryuichi Aoyagi
  • Naoki Kaneko
  • Atsushi Doi
  • Cory A Perugino
  • Emanuel Della-Torre
  • Takako Saeki
  • Yasuharu Sato
  • Hidetaka Yamamoto
  • Tamotsu Kiyoshima
  • John H Stone
  • Shiv Pillai
  • Seiji Nakamura
  • 全て表示

記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.jaci.2022.03.034

BACKGROUND: How T follicular (Tfh) cells contribute to many different B-cell class-switching events during T cell-dependent immune responses has been unclear. Diseases with polarized isotype switching offer a unique opportunity for the exploration of Tfh subsets. Secondary and tertiary lymphoid organs (SLOs and TLOs) in patients with elevated tissue expression levels of IgE (Kimura's disease, KD) and those of IgG4 (IgG4-related disease, IgG4-RD) can provide important insights regarding cytokine expression by Tfh cells. OBJECTIVE: To identify disease-specific Tfh cell subsets in SLOs and TLOs expressing IL-10 or IL-13 and thus identify different cellular drivers of class switching in two distinct types of fibrotic disorders: allergic fibrosis (driven by type 2 immune cells) and inflammatory fibrosis (driven by cytotoxic T lymphocytes). METHODS: Single-cell RNA-sequencing, in situ sequencing, and multi-color immunofluorescence analysis was used to investigate B cells, Tfh cells and infiltrating type 2 cells in lesion tissues from patients with KD or IgG4-RD. RESULTS: Infiltrating Tfh cells in TLOs from IgG4-RD were divided into six main clusters. We encountered abundant infiltrating IL-10-expressing LAG3+ Tfh cells in patients with IgG4-RD. Furthermore, we found that infiltrating AID+CD19+B cells expressing IL-4, IL-10, and IL-21 receptors correlated with IgG4 expression. In contrast, we found that infiltrating IL-13-expressing Tfh cells were abundant in affected tissues from patients with KD. Moreover, we observed few infiltrating IL-13-expressing Tfh cells in tissues from patients with IgG4-RD, despite high serum levels of IgE (but low IgE in the disease lesions). Cytotoxic T cells were abundant in IgG4-RD, and in contrast Type 2 immune cells were abundant in KD. CONCLUSIONS: This single-cell dataset revealed a novel subset of IL10+LAG3+Tfh cells infiltrating the affected organs of IgG4-RD patients. In contrast, IL13+Tfh cells and type 2 immune cells infiltrated those of KD patients.

リンク情報
DOI
https://doi.org/10.1016/j.jaci.2022.03.034
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/35568079
ID情報
  • DOI : 10.1016/j.jaci.2022.03.034
  • PubMed ID : 35568079

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