Role of RANK-L as a potential inducer of ILC2-mediated type 2 inflammation in chronic rhinosinusitis with nasal polyps

Noriko Ogasawara, Julie A. Poposki, Aiko I. Klingler, Bruce K. Tan, Kathryn E. Hulse, Whitney W. Stevens, Anju T. Peters, Leslie C. Grammer, Kevin C. Welch, Stephanie S. Smith, David B. Conley, Joseph R. Raviv, Pejman Soroosh, Ken ichi Takano, Tetsuo Himi, Robert C. Kern, Robert P. Schleimer, Atsushi Kato*

*Corresponding author for this work

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by type 2 inflammation with accumulation of activated group 2 innate lymphoid cells (ILC2s) and elevation of thymic stromal lymphopoietin (TSLP). A member of the TNF superfamily (TNFSF), TNFSF15, is known to induce the production of type 2 cytokines in ILC2s. Although ILC2s have been implicated in CRSwNP, the presence and role of TNFSFs in ILC2-mediated type 2 inflammation in CRSwNP has not been elucidated. Here, we investigate the involvement of TNFSFs in ILC2-mediated type 2 inflammation in CRSwNP. We found that receptor activator of NF-κB (RANK) ligand (RANK-L (TNFSF11)) was significantly elevated in nasal polyps (NPs), and that the receptor of RANK-L, RANK, was expressed on ILC2s in human peripheral blood and NPs. An agonistic antibody against RANK induced production of type 2 cytokines in human ILC2s, and TSLP significantly enhanced this reaction. The membrane-bound RANK-L was detected mainly on CD45 + immune cells, including TH2 cells in NPs. The co-culture of NP-derived ILC2s and TH2 cells significantly enhanced production of type 2 cytokines, and anti-RANK-L monoclonal antibody suppressed this enhancement. In conclusion, RANK-L, together with TSLP, may play an inductive role in the ILC2-mediated type 2 inflammation in CRSwNP.

Original languageEnglish (US)
Pages (from-to)86-95
Number of pages10
JournalMucosal Immunology
Volume13
Issue number1
DOIs
StatePublished - Jan 1 2020

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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