PT  - JOURNAL ARTICLE
AU  - Katrin Milger
AU  - Yingyan Yu
AU  - Eva Brudy
AU  - Martin Irmler
AU  - Melanie Königshoff
AU  - Frank Reichenberger
AU  - Jürgen Behr
AU  - Oliver Eickelberg
AU  - Susanne Krauss-Etschmann
TI  - The role of CCR2<sup>+</sup>CD4<sup>+</sup>T cells in lung fibrosis
DP  - 2014 Sep 01
TA  - European Respiratory Journal
PG  - 1732
VI  - 44
IP  - Suppl 58
4099  - http://erj.ersjournals.com/content/44/Suppl_58/1732.short
4100  - http://erj.ersjournals.com/content/44/Suppl_58/1732.full
SO  - Eur Respir J2014 Sep 01; 44
AB  - 1.INTRODUCTION: T cells have been suggested to play important roles in the development of lung fibrosis. C-C Chemokine receptor 2 (CCR2), the receptor of macrophage chemoattractant protein-1, is expressed by many immune cell types including T cells.The broad inhibition of CCR2-dependent signaling was shown to attenuate the development of experimental lung fibrosis. However, the role of CCR2+CD4+ T cells in lung fibrosis is unknown.2.OBJECTIVES: To investigate the phenotype and function of CCR2+CD4+ T cells using the bleomycin-induced lung fibrosis model and BALF samples from adult patients with lung fibrosis.3.RESULTS: After bleomycin instillation mice were analysed every 3rd day by FACS: CCR2+CD4+ T cells in lung and BALF increased during the fibrosis progress, peaking at day 12 after bleomycin instillation. Therefore, pulmonary CCR2+ and CCR2-CD4+ T cells were sorted at day 12 by FACS for transcriptomic profiling. This revealed the most upregulated transcription factor and cytokine were FoxP3 and IL-10, suggesting a regulatory phenotype. A suppressor assay showed that CCR2+ but not CCR2-CD4+ T cells, inhibited the proliferation of T effector cells. Adoptive transfer of CCR2+CD4+ T cells at day 2 after bleomycin, led to reduced inflammation and fibrosis at day 12. In BAL samples from human IPF patients, CCR2+CD4+ T cells were increased compared to controls and showed a higher expression of Treg markers FoxP3 and CD25 than CCR2-CD4+ T cells.4.CONCLUSION: Pulmonary CCR2+CD4+ T cells increased in experimental lung fibrosis and have an immunosuppressive function. During the early phase, CCR2+CD4+ T cells have a protective effect on fibrosis development. A similar phenotype of CCR2+CD4+ T cells was found in BALF of IPF patients.