Group 2 innate lymphoid cells are elevated and activated in chronic rhinosinusitis with nasal polyps

Immun Inflamm Dis. 2017 Sep;5(3):233-243. doi: 10.1002/iid3.161. Epub 2017 Apr 19.

Abstract

Background: Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is characterized by type 2 inflammation with high levels of Th2 cytokines. Although T helper cytokines are released from T cells, innate lymphoid cells (ILC) are also known to produce high levels of the same cytokines. However, the presence of various types of ILC in CRS is poorly understood.

Objective: The objective of this study was to fully characterize the presence of all ILC subsets in CRS and to identify phenotypical differences of group 2 ILC (ILC2) in CRSwNP compared to ILC2 from non-type 2 inflamed areas.

Methods: We investigated the presence of ILC subsets in peripheral blood mononuclear cells (PBMC) from healthy subjects, tonsil tissue, ethmoid tissue from control subjects and patients with non-polypoid CRS (CRSsNP) and CRSwNP, as well as nasal polyp (NP) tissue from CRSwNP by flow cytometry. Sorted ILC2 were cultured in the presence and absence of IL-33 and production of IL-5 and IL-13 was assessed by Luminex.

Results: We found that all ILC subsets were present in NP but ILC2 were dominant and significantly elevated compared to PBMC, tonsil, CRSsNP, and normal sinus tissue. We also found that inducible T-cell co-stimulator (ICOS) and side scatter were increased and CD127 was down-regulated in ILC2 from NP compared to blood or tonsil ILC2. Thymic stromal lymphopoietin, IL-7, and IL-33 were able to down-regulate expression of CD127 and increase side scatter in blood ILC2. Furthermore, sorted NP ILC2 but not blood ILC2 spontaneously released type 2 cytokines including IL-5 and IL-13.

Conclusions and clinical relevance: These results suggest that ILC2 are not only elevated but also activated in CRSwNP in vivo and that ILC2 may play important roles in the type 2 inflammation in CRSwNP.

Keywords: Chronic rhinosinusitis; ILC2; Type 2 inflammation; innate lymphoid cells; nasal polyp.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Chronic Disease
  • Cytokines / immunology
  • Female
  • Humans
  • Immunity, Innate*
  • Interleukin-7 Receptor alpha Subunit / immunology
  • Lymphocytes* / immunology
  • Lymphocytes* / pathology
  • Male
  • Middle Aged
  • Nasal Polyps* / immunology
  • Nasal Polyps* / pathology
  • Rhinitis* / immunology
  • Rhinitis* / pathology
  • Sinusitis* / immunology
  • Sinusitis* / pathology

Substances

  • Cytokines
  • Interleukin-7 Receptor alpha Subunit