Peripheral depletion of NK cells and imbalance of the Treg/Th17 axis in idiopathic pulmonary fibrosis patients

Domenico Galati, Marina De Martino, Annamaria Trotta, Gaetano Rea, Dario Bruzzese, Gaetano Cicchitto, Anna Agnese Stanziola, Maria Napolitano, Alessandro Sanduzzi, Marialuisa Bocchino

Research output: Contribution to journalArticlepeer-review

Abstract

The immune response plays an unsettled role in the pathogenesis of idiopathic pulmonary fibrosis (IPF), the contribution of inflammation being controversial as well. Emerging novel T cell sub-populations including regulatory T lymphocytes (Treg) and interleukin (IL)-17 secreting T helper cells (Th17) may exert antithetical actions in this scenario. Phenotype and frequency of circulating immune cell subsets were assessed by multi-parametric flow cytometry in 29 clinically stable IPF patients and 17 healthy controls. The interplay between Treg lymphocytes expressing transforming growth factor (TGF)-β and Th17 cells was also investigated. Proportion and absolute number of natural killer (NK) cells were significantly reduced in IPF patients in comparison with controls (p+CD4+CD25highFoxp-3+ cells were significantly increased in IPF patients (p=0.000). As in controls, almost the totality of cells (>90%) expressed TGF-β upon stimulation. Interestingly, the frequency of Th17 cells was significantly compromised in IPF patients (p=0.000) leading to an increased TGF-β/IL-17 ratio (4.2±2.3 vs 0.5±0.3 in controls, p=0.000). Depletion of NK and Th17 cells along with a not compromised Treg compartment delineate the existence of an "immune profile" that argue against the recent hypothesis of IPF as an autoimmune disease. Our findings along with the imbalance of the Treg/Th17 axis more closely suggest these immune perturbations to be similar to those observed in cancer. Clinical relevance, limitations and perspectives for future research are discussed.

Original languageEnglish
Pages (from-to)119-126
Number of pages8
JournalCytokine
Volume66
Issue number2
DOIs
Publication statusPublished - 2014

Keywords

  • Flow cytometry
  • IPF
  • NK cells
  • Regulatory T cells
  • Th17 cells

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Hematology
  • Biochemistry
  • Molecular Biology

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