| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 3257196 | Clinical Immunology | 2011 | 11 Pages |
T cells, particularly those producing IL-4, are implicated in inflammation-mediated fibrosis. In our phase I/IIa open-label pilot study in 15 patients with scleroderma-interstitial lung disease (SSc-ILD), high-dose imatinib treatment showed modest improvement in lung function and skin score, but with several adverse events. Here, we investigated T cell phenotype and cytokine production in bronchoalveolar lavage (BAL) from patients enrolled in this trial. We found that IL-4+ T cells showed a stronger correlation with ground glass opacity (GGO) than fibrosis scores on lung high-resolution computer tomography scans. Frequencies of IL-4+ T cells also discriminated patients with high (≥ 20) versus low (< 20) GGO scores. Functional annotation clustering of proteins that correlated with T cells identified two major clusters that belonged to immune/inflammatory and wounding response. Repeat analyses after 1 year of treatment in 10 BAL samples, one each from the right middle and lower lobes of lung from 5 patients, showed that post-imatinib, IL-4+ T cells were profoundly reduced but CD4+ T cells increased, except in one patient who showed worsening of SSc-ILD. Post-imatinib increase in CD4+ T cells correlated with soluble ICAM-3 and PECAM-1 levels in BAL, which associated with the lack of worsening in SSc-ILD. Thus, imatinib might confer its therapeutic effect in fibrosis via re-directing T cell responses from type 2 to other, non-type 2 cytokine producing CD4+ T cells.
► IL-4+ T cells are reduced in lungs of scleroderma patients treated with imatinib. ► Lung IL-4+ T cells correlate with ground glass opacity in scleroderma patients. ► IL-4+ T cells in lung correlate with inflammatory and wounding response proteins. ► IL-4–CD4+ T cells, ICAM3 and PECAM1 increase in BAL after imatinib treatment. ► T cell subsets substantially differ between different lobes of lung in scleroderma.
