title: Skewed Lung CCR4 to CCR6 CD4+T Cell Ratio in Idiopathic Pulmonary Fibrosis Is Associated with Pulmonary Function.
abstract: BACKGROUND
  Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease. While it has been suggested that T cells may contribute to IPF pathogenesis, these studies have focused primarily on T cells outside of the pulmonary interstitium. Thus, the role of T cells in the diseased lung tissue remains unclear.
  
  
  OBJECTIVE
  To identify whether specific CD4+T cell subsets are differentially represented in lung tissue from patients with IPF.
  
  
  METHODS
  CD4+T cell subsets were measured in lung tissue obtained from patients with IPF at the time of lung transplantation, and from age- and gender-matched organ donors with no known lung disease. Subsets were identified by their surface expression of CCR4, CCR6, and CXCR3 chemokine receptors. CD4+T cell subsets were correlated with measurements of lung function obtained prior to transplantation.
  
  
  RESULTS
  Compared to controls, IPF patients had a higher proportion of lung CD4+T cells, a higher proportion of CCR4+CD4+T cells, and a lower proportion of CCR6+CD4+T cells. The increase in CCR4+CD4+T cells in IPF lung tissue was not due to increased Tregs. Intriguingly, the increase in the ratio of CCR4+cells to CCR6+cells correlated significantly with better lung function.
  
  
  CONCLUSIONS
  Our findings suggest a new paradigm that not all T cell infiltrates in IPF lungs are detrimental, but instead, specialized subsets may actually be protective. Thus, augmentation of the chemokines that recruit protective T cells, while blocking chemokines that recruit detrimental T cells, may constitute a novel approach to IPF therapy.
authors.affiliation: Section of Pulmonary and Critical Care, Department of Medicine, University of Chicago , Chicago, IL , USA.
authors.forename: Ayodeji
authors.initials: A
authors.lastname: Adegunsoye
authors.affiliation: Section of Pulmonary and Critical Care, Department of Medicine, University of Chicago, Chicago, IL, USA; Committee on Immunology, University of Chicago, Chicago, IL, USA.
authors.forename: Cara L
authors.initials: CL
authors.lastname: Hrusch
authors.affiliation: Section of Pulmonary and Critical Care, Department of Medicine, University of Chicago , Chicago, IL , USA.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Bonham
authors.affiliation: Section of Pulmonary and Critical Care, Department of Medicine, University of Chicago , Chicago, IL , USA.
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Jaffery
authors.affiliation: Section of Pulmonary and Critical Care, Department of Medicine, University of Chicago , Chicago, IL , USA.
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Blaine
authors.affiliation: Section of Pulmonary and Critical Care, Department of Medicine, University of Chicago , Chicago, IL , USA.
authors.forename: Meghan
authors.initials: M
authors.lastname: Sullivan
authors.affiliation: Section of Pulmonary and Critical Care, Department of Medicine, University of Chicago , Chicago, IL , USA.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Churpek
authors.affiliation: Section of Pulmonary and Critical Care, Department of Medicine, University of Chicago , Chicago, IL , USA.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Strek
authors.affiliation: Section of Pulmonary and Critical Care, Department of Medicine, University of Chicago , Chicago, IL , USA.
authors.forename: Imre
authors.initials: I
authors.lastname: Noth
authors.affiliation: Section of Pulmonary and Critical Care, Department of Medicine, University of Chicago, Chicago, IL, USA; Committee on Immunology, University of Chicago, Chicago, IL, USA.
authors.forename: Anne I
authors.initials: AI
authors.lastname: Sperling
keywords: CD4; T cells; chemokine receptors; idiopathic pulmonary fibrosis; lung function