The mucosal immune response to laryngopharyngeal reflux

Louisa E N Rees, Laszlo Pazmany, Danuta Gutowska-Owsiak, Charlotte F. Inman, Anne Phillips, Christopher R. Stokes, Nikki Johnston, Jamie A. Koufman, Gregory Postma, Michael Bailey, Martin A. Birchall

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Rationale: Laryngopharyngeal reflux (LPR) affects up to 20% of Western populations. Although individual morbidity is usually moderate, treatment costs are high and there are associations with other diseases, including laryngeal cancer. To date, there have been no studies of the mucosal immune response to this common inflammatory disease. Objectives: To determine the mucosal immune response to LPR. Methods: We performed a prospective immunologic study of laryngeal biopsies from patients with LPR and control subjects (n = 12 and 11, respectively), and of primary laryngeal epithelial cells in vitro. Measurements and Main Results: Quantitative multiple-color immunofluorescence, using antibodies for lymphocytes (CD4, CD8, CD3, CD79, CD161), granulocytes (CD68, EMBP), monocytic cells (CD68, major histocompatibility complex [MHC] class II), and classical and nonclassical MHC (I, II, β2-microglobulin, CD1d). Univariate and multivariate analysis and colocalization measurements were applied. There was an increase in percentage area of mucosal CD8+ cells in the epithelium (P < 0.005), whereas other leukocyte and granulocyte antigens were unchanged. Although epithelial MHC class I and II expression was unchanged by reflux, expression of the nonclassical MHC molecule CD1d increased (P < 0.05, luminal layers). In vitro, laryngeal epithelial cells constitutively expressed CD1d. CD1d and MHC I expression were inversely related in all subjects, in a pattern which appears to be unique to the upper airway. Colocalization of natural killer T (NKT) cells with CD1d increased in patients (P < 0.01). Conclusions: These data indicate a role for the CD1d-NKT cell axis in response to LPR in humans. This represents a useful target for novel diagnostics and treatments in this common condition.

Original languageEnglish (US)
Pages (from-to)1187-1193
Number of pages7
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume177
Issue number11
DOIs
StatePublished - Jun 1 2008
Externally publishedYes

Keywords

  • CD1d
  • Epithelial cells
  • Laryngopharyngeal reflux
  • Natural killer T cells

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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    Rees, L. E. N., Pazmany, L., Gutowska-Owsiak, D., Inman, C. F., Phillips, A., Stokes, C. R., Johnston, N., Koufman, J. A., Postma, G., Bailey, M., & Birchall, M. A. (2008). The mucosal immune response to laryngopharyngeal reflux. American Journal of Respiratory and Critical Care Medicine, 177(11), 1187-1193. https://doi.org/10.1164/rccm.200706-895OC