Cyclosporin A indirectly attenuates activation of group 2 innate lymphoid cells in papain-induced lung inflammation

Cell Immunol. 2018 Jan:323:33-40. doi: 10.1016/j.cellimm.2017.10.010. Epub 2017 Oct 27.

Abstract

Cyclosporin A (CsA) is a well-known immunosuppressant that is used against steroid-resistant asthma. Group 2 innate lymphoid cells (ILC2s) and type 2 helper T (Th2) cells produce Th2 cytokines including IL-5 and play important roles in asthma pathogenesis. Here, we studied the effects of CsA in allergen-induced lung inflammation in mice and found that CsA decreased the number of lung ILC2s and attenuated papain-induced activation of ILC2s accompanied with IL-5 expression. The ILC2 suppression mediated by CsA was not observed in culture or in lymphocyte-deficient Rag2-/- mice. Thus, we propose a new suppressive effect of CsA, i.e., administration of CsA indirectly suppresses maintenance and activation of lung ILC2s in addition to direct suppression of T-cell activation and cytokine production.

Keywords: Asthma; Cyclosporin A; ILC2; Th2 cytokine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens
  • Animals
  • Asthma / immunology
  • Asthma / metabolism
  • Cyclosporine / metabolism
  • Cyclosporine / pharmacology*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Immunity, Innate / immunology
  • Lung / immunology
  • Lymphocyte Activation
  • Lymphocytes / drug effects*
  • Lymphocytes / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Papain / pharmacology
  • Pneumonia / drug therapy*
  • Pneumonia / metabolism
  • Th2 Cells / drug effects
  • Th2 Cells / immunology

Substances

  • Allergens
  • Cytokines
  • Cyclosporine
  • Papain