Predominant infiltration of monocytes in chronic graft-versus-host disease

Pathogenesis of chronic graft-versus-host disease (cGVHD) is largely unknown. It is important to determine the responsible cell types and the factors that play roles to recruit these cells into sites of disease. We examined whether monocytes and chemokine fractalkine/receptor CX3CR1 axis might be involved. We found that the absolute number of CX3CR1 + monocytes in the blood was significantly decreased in patients with severe cGVHD. Immunohistochemical staining revealed the extensive infiltration of CD 14 + cells as well as strong expression of fractalkine in the cGVHD skin. The number of infiltrated CD14+ cells on the margin of fractatkine+ epidermis was larger in cGVHD skin compared to that of acute graft-versus-host disease, whereas no difference was observed in CD3 + T cells. These results suggest that CX3CR1+ monocytes may be recruited from the circulation to the fractalkine + epidermis in cGVHD, and highlight these cells and this chemokine/receptor axis as additional targets for cGVHD therapy.

慢性移植物抗宿主病（cGVHD）的发病机制在很大程度上尚不明确。确定起作用的细胞类型以及促使这些细胞募集到疾病部位的因素是很重要的。我们研究了单核细胞以及趋化因子分形趋化因子/受体CX3CR1轴是否可能参与其中。我们发现，在重度cGVHD患者中，血液中CX3CR1 +单核细胞的绝对数量显著减少。免疫组化染色显示，在cGVHD皮肤中CD14 +细胞广泛浸润，并且分形趋化因子大量表达。与急性移植物抗宿主病相比，在cGVHD皮肤中，分形趋化因子 +表皮边缘浸润的CD14 +细胞数量更多，而在CD3 + T细胞中未观察到差异。这些结果表明，在cGVHD中，CX3CR1 +单核细胞可能从循环中被募集到分形趋化因子 +表皮，并强调这些细胞以及这种趋化因子/受体轴可作为cGVHD治疗的额外靶点。