Enhanced innate type 2 immune response in peripheral blood from patients with asthma

J Allergy Clin Immunol. 2014 Sep;134(3):671-678.e4. doi: 10.1016/j.jaci.2014.06.024.


Background: In mice, group 2 innate lymphoid cells (ILC2s) likely mediate helminth immunity, inflammation, and tissue repair and remodeling. However, the involvement of ILC2s in human diseases, such as asthma, is not well understood.

Objectives: The goals of this study were to investigate whether peripheral blood specimens can be used to monitor innate type 2 immunity in human subjects and to examine whether ILC2s are involved in human asthma.

Methods: PBMCs from subjects with allergic asthma (AA), subjects with allergic rhinitis (AR), or healthy control (HC) subjects were cultured in vitro with IL-25 or IL-33. Flow cytometry and cell sorting were used to identify, isolate, and quantitate ILC2s in PBMCs.

Results: Human PBMCs produced IL-5 and IL-13 when stimulated with IL-33 or IL-25 in the presence of IL-2 without antigens. In addition, IL-7 or thymic stromal lymphopoietin were able to replace IL-2. The cell population with phenotypic ILC2 characteristics, lineage(-)CD127(+)CRTH2(+) cells, responded to IL-33 and produced large quantities of IL-5 and IL-13 but undetectable levels of IL-4. PBMCs from subjects with AA produced significantly larger amounts of IL-5 and IL-13 in response to IL-25 or IL-33 than from subjects with AR or HC. The prevalence of ILC2s in blood was greater in the AA group than in the AR group or the HC group.

Conclusions: Innate type 2 immune responses are increased in asthma but not in AR, suggesting potential differences in the immunopathogenesis of these diseases. Peripheral blood is useful for evaluating innate type 2 immunity in humans.

Keywords: IL-13; IL-25; IL-33; IL-5; ILC2; allergy; asthma; innate immunity.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Asthma / diagnosis
  • Asthma / immunology*
  • Blood Circulation
  • Cell Differentiation
  • Cell Separation
  • Cells, Cultured
  • Female
  • Flow Cytometry
  • Humans
  • Immunity, Innate
  • Interleukin-7 Receptor alpha Subunit / metabolism
  • Interleukins / immunology
  • Lymphocytes / immunology*
  • Male
  • Middle Aged
  • Receptors, Immunologic / metabolism
  • Receptors, Prostaglandin / metabolism
  • Rhinitis, Allergic / diagnosis
  • Rhinitis, Allergic / immunology*
  • Th2 Cells / immunology


  • Interleukin-7 Receptor alpha Subunit
  • Interleukins
  • Receptors, Immunologic
  • Receptors, Prostaglandin
  • prostaglandin D2 receptor