Lung-Infiltrating Foxp3+ Regulatory T Cells Are Quantitatively and Qualitatively Different during Eosinophilic and Neutrophilic Allergic Airway Inflammation but Essential To Control the Inflammation

J Immunol. 2017 Dec 15;199(12):3943-3951. doi: 10.4049/jimmunol.1700211. Epub 2017 Nov 1.

Abstract

Understanding functions of Foxp3+ regulatory T cells (Tregs) during allergic airway inflammation remains incomplete. In this study, we report that, during cockroach Ag-induced allergic airway inflammation, Foxp3+ Tregs are rapidly mobilized into the inflamed lung tissues. However, the level of Treg accumulation in the lung was different depending on the type of inflammation. During eosinophilic airway inflammation, ∼30% of lung-infiltrating CD4 T cells express Foxp3, indicative of Tregs. On the contrary, only ∼10% of infiltrating CD4 T cells express Foxp3 during neutrophilic airway inflammation. Despite the different accumulation, the lung inflammation and inflammatory T cell responses were aggravated following Treg depletion, regardless of the type of inflammation, suggesting regulatory roles for Tregs. Interestingly, however, the extent to which inflammatory responses are aggravated by Treg depletion was significantly greater during eosinophilic airway inflammation. Indeed, lung-infiltrating Tregs exhibit phenotypic and functional features associated with potent suppression. Our results demonstrate that Tregs are essential regulators of inflammation, regardless of the type of inflammation, although the mechanisms used by Tregs to control inflammation may be shaped by environmental cues available to them.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / toxicity
  • Allergens / administration & dosage
  • Allergens / immunology
  • Alum Compounds / administration & dosage
  • Alum Compounds / toxicity
  • Alveolitis, Extrinsic Allergic / etiology
  • Alveolitis, Extrinsic Allergic / immunology*
  • Alveolitis, Extrinsic Allergic / pathology
  • Animals
  • Cockroaches / immunology
  • Disease Models, Animal
  • Forkhead Transcription Factors / analysis
  • Freund's Adjuvant / administration & dosage
  • Freund's Adjuvant / toxicity
  • Gene Expression Profiling
  • Genes, Reporter
  • Immunophenotyping
  • Inflammation
  • Insect Proteins / administration & dosage
  • Insect Proteins / immunology
  • Lung / immunology*
  • Lung / pathology
  • Mice, Inbred C57BL
  • Neutrophil Infiltration / immunology*
  • Pulmonary Eosinophilia / etiology
  • Pulmonary Eosinophilia / immunology*
  • Pulmonary Eosinophilia / pathology
  • Specific Pathogen-Free Organisms
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Adjuvants, Immunologic
  • Allergens
  • Alum Compounds
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Insect Proteins
  • aluminum sulfate
  • Freund's Adjuvant