CC-chemokine receptor 6 and its ligand macrophage inflammatory protein 3alpha might be involved in the amplification of local necroinflammatory response in the liver.
It is not fully understood how antigen-specific or-nonspecific T cells migrate into the liver in various liver diseases. Macrophage inflammatory protein (MIP)-3alpha is a chemokine that is expressed mostly in the liver, and the receptor CCR6 is reported to be expressed on memory T cells. In the present study, we focused on the expression of CCR6 on T cells from peripheral blood (PB) and inflamed liver, and analyzed the involvement of MIP-3alpha and CCR6 in the immunopathogenesis of liver diseases. Intrahepatic T cells showed significantly (P <.0001) higher percentages of CCR6(+)CD4(+) T cells compared with PB, which is significantly (P =.037) correlated with the necroinflammatory response in the liver. Most of intrahepatic CCR6(+)CD4(+) cells were also positive for CCR5, which is known to express on T-helper 1 cells. MIP-3alpha was stained in the cells located near piecemeal necrosis, where dendritic cells (DCs) are often observed, and coculture of activated DCs with apoptotic cells induced MIP-3alpha production from the DCs. These data suggest that MIP-3alpha is produced by periportal DCs and/or macrophages after necroinflammatory response, leading to the recruitment of activated T cells into the liver. This process could be important to augment the local immune response in the livers of various liver diseases. The finding might be important not only for the understanding of immunopathogenesis of liver diseases but also for the therapeutic strategy to control the local immune response in the liver.
Shimizu
Y
Y
The Third Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan. yukihiro-tym@cc.umin.ac.jp
Murata
H
H
Kashii
Y
Y
Hirano
K
K
Kunitani
H
H
Higuchi
K
K
Watanabe
A
A
D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D017209:Apoptosis; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000235:genetics / Q000502:physiology*; D003713:Dendritic Cells / Q000378:metabolism; D005434:Flow Cytometry; D006505:Hepatitis / Q000473:pathology* / Q000503:physiopathology*; D006801:Humans; D007150:Immunohistochemistry; D037181:Lectins, C-Type; D008024:Ligands; D008099:Liver / Q000473:pathology / Q000503:physiopathology; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000502:physiology*; D009336:Necrosis; D010587:Phagocytosis / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D019713:Receptors, CCR5 / Q000378:metabolism; D054399:Receptors, CCR6; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D054418:Chemokine CCL20; D019742:Chemokines, CC; D037181:Lectins, C-Type; D008024:Ligands; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D019713:Receptors, CCR5; D054399:Receptors, CCR6; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D000099192:CD69 Antigens; C108355:CCL20 protein, human; C106311:CCR6 protein, human; C515187:CXCR3 protein, human