β2-adrenergic stimulation of dendritic cells favors IL-10 secretion by CD4+ T cells

Immunol Res. 2017 Dec;65(6):1156-1163. doi: 10.1007/s12026-017-8966-3.

Abstract

Adrenergic receptor agonists and antagonists are extensively used as drugs in medicine for a broad spectrum of indications. We examined the consequences of β2-adrenergic stimulation of murine dendritic cells (DCs) on CD4+ T cell activation. We demonstrated in vitro that treatment of LPS-matured DCs with the β2-agonist salbutamol reduced their ability to trigger OT-II T cell proliferation specific for ovalbumin antigen. Salbutamol also induced a decrease in MHC class II molecule expression by DC through Gi protein activation. Co-culture of CD4+ T cells with salbutamol-conditioned mature DC impaired TNFα and IL-6 secretion while preserving IL-10 production by T cells. Using a vaccination protocol in mice, we showed that salbutamol favored IL-10-producing CD4+ T cells. None of these effects was observed when working with β2-adrenoreceptor deficient mice. Finally, we suggest that β2-adrenergic stimulation of DC could be an interesting way to shape CD4+ T cell responses for the purposes of immunotherapy.

Keywords: CD4+ T lymphocyte; Dendritic cell; IL-10; Salbutamol; β2-adrenergic receptor.

MeSH terms

  • Adrenergic beta-2 Receptor Agonists / pharmacology*
  • Albuterol / pharmacology*
  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / transplantation
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Coculture Techniques
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Interleukin-10 / metabolism
  • Lipopolysaccharides / immunology
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Adrenergic, beta-2 / genetics
  • Receptors, Adrenergic, beta-2 / metabolism*

Substances

  • Adrenergic beta-2 Receptor Agonists
  • Lipopolysaccharides
  • Receptors, Adrenergic, beta-2
  • Interleukin-10
  • Albuterol