Skewed Lung CCR4 to CCR6 CD4+ T Cell Ratio in Idiopathic Pulmonary Fibrosis Is Associated with Pulmonary Function

Ayodeji Adegunsoye, Cara L. Hrusch, Catherine A. Bonham, Mohammad R. Jaffery, Kelly M. Blaine, Meghan Sullivan, Matthew M. Churpek, Mary E. Strek, Imre Noth, Anne I. Sperling

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. To identify whether specific CD4(+) T cell subsets are differentially represented in lung tissue from patients with IPF. 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. 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. 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.