Distinct roles of α7 nAChRs in antigen-presenting cells and CD4+ T cells in the regulation of T cell differentiation

Masato Mashimo, Masayo Komori, Yuriko Y. Matsui, Mami X. Murase, Takeshi Fujii, Shiori Takeshima, Hiromi Okuyama, Shiro Ono, Yasuhiro Moriwaki, Hidemi Misawa, Koichiro Kawashima

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

It is now apparent that immune cells express a functional cholinergic system and that α7 nicotinic acetylcholine receptors (α7 nAChRs) are involved in regulating T cell differentiation and the synthesis of antigen-specific antibodies and proinflammatory cytokines. Here, we investigated the specific function α7 nAChRs on T cells and antigen presenting cells (APCs) by testing the effect of GTS-21, a selective α7 nAChR agonist, on differentiation of CD4+ T cells from ovalbumin (OVA)-specific TCR transgenic DO11.10 mice activated with OVA or OVA peptide323−339 (OVAp). GTS-21 suppressed OVA-induced antigen processing-dependent development of CD4+ regulatory T cells (Tregs) and effector T cells (Th1, Th2, and Th17). By contrast, GTS-21 up-regulated OVAp-induced antigen processing-independent development of CD4+ Tregs and effector T cells. GTS-21 also suppressed production of IL-2, IFN-γ, IL-4, IL-17, and IL-6 during OVA-induced activation but, with the exception IL-2, enhanced their production during OVAp-induced activation. In addition, during antigen-nonspecific, APC-independent anti-CD3/CD28 antibody-induced CD4+ polyclonal T cell activation in the presence of respective polarizing cytokines, GTS-21 promoted development of all lineages, which indicates that GTS-21 also acts via α7 nAChRs on T cells. These results suggest 1) that α7 nAChRs on APCs suppress CD4+ T cell activation by interfering with antigen presentation through inhibition of antigen processing; 2) that α7 nAChRs on CD4+ T cells up-regulate development of Tregs and effector T cells; and that α7 nAChR agonists and antagonists could be potentially useful agents for immune response modulation and enhancement.

Original languageEnglish
Article number1102
JournalFrontiers in Immunology
Volume10
Issue numberMAY
DOIs
Publication statusPublished - 2019 Jan 1

    Fingerprint

Keywords

  • DO11. 10 mouse
  • GTS-21
  • Regulatory T cells
  • Th1
  • Th17
  • Th2
  • α7 nAChR

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Mashimo, M., Komori, M., Matsui, Y. Y., Murase, M. X., Fujii, T., Takeshima, S., Okuyama, H., Ono, S., Moriwaki, Y., Misawa, H., & Kawashima, K. (2019). Distinct roles of α7 nAChRs in antigen-presenting cells and CD4+ T cells in the regulation of T cell differentiation. Frontiers in Immunology, 10(MAY), [1102]. https://doi.org/10.3389/fimmu.2019.01102