Pivotal role of duct epithelia in salivary gland GVHD

Although salivary glands are one of the target organs in graft-versus host disease (GVHD), mechanism of disease-related tissue injury has been poorly understood. To investigate it, we employed rat GVHD model including irradiation and donor cell transfer. Immunostaining revealed that submandibular and parotid, but not sublingual glands showed acinar reduction whereas ducts were almost intact. Ductal area of sublingual glands was significantly smaller than those of submandibular and parotid glands. Ductal epithelial cells upregulated expression of class II major histocompatibility complex antigens overtime. This expression preceded donor cell infiltration. Donor cell infiltration was preferentially found in ductal area at the early phase of the disease. While ductal epithelial cells exhibited upregulated mRNA expression of Th1-type chemokines, infiltrating donor cells exhibited their receptors CXCR3 and CCR5. These results suggest ductal epithelial cells have a pivotal role in the progression of GVHD.