Journal Article

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

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

2020

Overview

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.

• Publisher: Elsevier Inc,Nature Publishing Group US,Elsevier Limited
• Subject: Adolescent / Adult / Aged / Aged, 80 and over / Allergology / Antibodies / Biomedical and Life Sciences / Biomedicine / CD45 antigen / Cell culture / Cells, Cultured / Chronic Disease / Cytokines / Cytokines - metabolism / Female / Gastroenterology / Helper cells / Humans / Immunity, Innate / Immunology / Inflammation / Inflammation - immunology / Lymphocytes - immunology / Lymphocytes T / Lymphoid cells / Male / Middle Aged / Monoclonal antibodies / Nasal Polyps - immunology / NF-κB protein / Peripheral blood / Polyps / RANK Ligand - metabolism / Rhinitis / Rhinitis - immunology / Rhinosinusitis / Sinusitis / Sinusitis - immunology / Th2 Cells - immunology / Th2 Cells - metabolism / Thymic stromal lymphopoietin / Thymus / TRANCE protein / Tumor necrosis factor / Young Adult