Conventional type 2 lung dendritic cells are potent inducers of follicular helper T cells in the asthmatic lung

• Sakurai Shogo

  Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine

• Furuhashi Kazuki

  Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine Department of Laboratory Medicine, Hamamatsu University School of Medicine

• Horiguchi Ryo

  Advanced Research Facilities and Services, Hamamatsu University School of Medicine

• Nihashi Fumiya

  Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine

• Yasui Hideki

  Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine

• Karayama Masato

  Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine

• Suzuki Yuzo

  Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine

• Hozumi Hironao

  Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine

• Enomoto Noriyuki

  Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine

• Fujisawa Tomoyuki

  Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine

• Nakamura Yutaro

  Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine

• Inui Naoki

  Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine

• Suda Takafumi

  Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine

Abstract

Background: Follicular helper T (Tfh) cells represent a unique subset of helper CD4⁺ T cells in lymphoid follicles. Recently, Tfh cells were shown to play an important role in asthma through B cell differentiation. Conventional lung DCs are classified into two major subsets: conventional type 1 (cDC1) and type 2 (cDC2). Although the two subsets are different in driving particular T cell responses, the subset that induces Tfh cells in the asthmatic lung primarily has yet to be fully elucidated. Methods: We evaluated Tfh cells, defined by the expression of CD4 and CXCR5, in HDM-challenged mice. Next, we characterized cDC1 and cDC2 purified from antigen-primed lung and examined their Tfh cell-inducing capacity. Additionally, the ability of lung DC-induced Tfh cells to cause germinal center B (GCB) cells to produce antigen-specific IgE was assessed. Results: In HDM-challenged mice, Bcl-6-expressing Tfh cells were significantly increased in the mediastinal lymph nodes. Lung cDC2, but not lung cDC1, increased after HDM priming, and cDC2 secreted larger amounts of IL-6 with higher ICOS-L expression than cDC1. In the co-cultures with OVA-specific naïve CD4⁺ T cells, cDC2 from OVA-primed lung induced Bcl-6-expressing Tfh cells more efficiently, together with larger amounts of IL-6 and IL-21, than cDC1. Blockage of IL-6 or ICOS-L significantly reduced Tfh cell induction. Finally, cDC2-induced Tfh cells enabled GCB cells to produce OVA-specific IgE. Conclusions: In asthmatic lung, cDC2 is the primary DC subset responsible for Tfh cell differentiation and plays an important role in humoral immunity in asthma by inducing Tfh cells.

Journal

• Allergology International

  Allergology International 70 (3), 351-359, 2021

  Japanese Society of Allergology

Keywords

• Bronchial asthma
• Conventional type 2 dendritic cells
• Follicular helper T cells
• Lung
• Mouse model

Details

• CRID: 1390570166645258496
• NII Article ID: 130008064053
• DOI: 10.1016/j.alit.2021.01.008
• ISSN: 14401592
• ISSN: 13238930
• Web Site: https://api.elsevier.com/content/article/PII:S1323893021000137?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S1323893021000137?httpAccept=text/plain
• Web Site: https://search.jamas.or.jp/link/ui/2022173662
• Text Lang: en
• Data Source:
  • JaLC
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed