IL-21 Is Increased in Nasal Polyposis and after Stimulation with Staphylococcus aureus Enterotoxin B

Int Arch Allergy Immunol. 2017;174(3-4):161-169. doi: 10.1159/000481435. Epub 2017 Nov 9.

Abstract

Background: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory disease associated with lymphoid aggregates and local IgE production related to Staphylococcus aureus enterotoxins. T-follicular helper cells and their effector cytokine interleukin (IL)-21 play an important role in germinal center proliferation.

Methods: IL-21 was determined on the mRNA level by qPCR in nasal tissue of 3 groups of patients: control (n = 17), chronic rhinosinusitis without nasal polyposis (CRSsNP; n = 23), and CRSwNP (n = 35). The expression of IL-21 by CD4+ T cells was analyzed in tissue at baseline and after 24-h stimulation of tissue fragments with S. aureus enterotoxin B (SEB) using flow cytometry. Finally, human nasal IL-21+CXCR5+CD4+ T cells were isolated and coincubated with human blood naive B cells to investigate their functionality.

Results: IL-21 mRNA expression was increased in the CRSwNP group (p < 0.05) compared to the control group, and B-cell lymphoma-6 and B-lymphocyte-induced maturation protein-1 were upregulated in CRSwNP versus CRSsNP. Furthermore, SEB was able to increase IL-21 mRNA expression significantly (p < 0.01) in nasal polyps. Flow cytometry revealed that the source of IL-21 was predominantly CD4+ T cells and that IL-21+CD4+ T cells were significantly increased in polyp tissue and further increased after SEB stimulation. Finally, tissue CXCR5+CD4+ T cells derived from nasal polyp tissue were able to induce maturation of human naive B cells.

Conclusions: IL-21- and IL-21-producing CD4+ T cells were increased in CRSwNP. In addition, SEB induced an increase in IL-21 and IL-21+CD4+ T cells, suggesting that S. aureus can modulate the function of Tfh cells in nasal polyps. We speculate that T-follicular helper cells and IL-21 are important in the pathophysiology of CRSwNP.

Keywords: Chronic rhinosinusitis; Germinal center; Interleukin-21; Nasal polyposis; T-follicular helper cell.

MeSH terms

  • Adult
  • B-Lymphocytes / immunology
  • Cell Differentiation
  • Cells, Cultured
  • Chronic Disease
  • Enterotoxins / immunology
  • Female
  • Germinal Center / immunology
  • Humans
  • Immunoglobulin E / blood
  • Interleukins / genetics
  • Interleukins / metabolism*
  • Male
  • Middle Aged
  • Nasal Polyps / immunology*
  • Receptors, CXCR5 / metabolism
  • Rhinitis / immunology*
  • Sinusitis / immunology*
  • Staphylococcal Infections / immunology*
  • Staphylococcus aureus / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology*

Substances

  • CXCR5 protein, human
  • Enterotoxins
  • Interleukins
  • Receptors, CXCR5
  • Immunoglobulin E
  • enterotoxin B, staphylococcal
  • interleukin-21