Diverse Activity of IL-17 + Cells in Chronic Skin and Mucosa Graft-Versus-Host Disease

Excessive inflammatory environment in a course of chronic graft-versus-host disease (cGvHD) is associated with T-cell trafficking into inflamed tissues. This study focused on the identification of IL-17-producing cells in the tissue biopsies of cGvHD patients. Forty-one biopsy specimens of cGvHD lesions of the skin ( n = 27), gastrointestinal tract ( n = 9) and oral mucosa ( n = 5), examined in 24 patients, were morphologically defined according to the NIH criteria and analyzed for the presence of cellular infiltrations including: IL-17 + , FOXP3 + and CCR6 + cells. IL-17 + cells were identified in 26/27 skin and in all gut and oral mucosa biopsies, being more frequent in mucosa lesions than in the skin (11/14 vs 14/26, respectively; NS: not significant). Double staining documented that CD138 + /IL-17 + cells were commonly seen in the gut than in the skin (5/8 vs 3/11, respectively; NS). In the skin, cells expressing trafficking receptor CCR6 + were more frequent than IL-17 + cells compared to the mucosa (23/26 vs 2/13, respectively; p < 0.0001). CCR6 was present on a majority of IL-17 + cells in all examined skin biopsies but only in 6 out of 11 digestive tract biopsies ( p = 0.0112). FOXP3 + cells were identified only in five patients (with mild lesions) at least in one biopsy. In this study group, results documented that local expansion of IL-17-producing cells in the digestive tract correlate with moderate and severe clinical symptoms of cGvHD, in contrast to the skin, where IL-17 + cells are rather scarcely present ( p = 0.0301) and the course of cGvHD is slowly progressing with final organ deterioration.