Accumulation of functional regulatory T cells in actively inflamed liver in mouse dendritic cell-based autoimmune hepatic inflammation.
Participation of Tregs in the generation of autoimmune hepatic inflammation (AHI) was examined using a newly established dendritic cell (DC)-based mouse model of hepatitis. The inflammatory activity of AHI peaked 21 days after DC vaccination. Forkhead box P3 (Foxp3) expression on day 21 was significantly increased in the liver but was decreased in the spleen. CD4(+)CD25(+) Tregs from the liver on day 21 showed inhibitory activity against the proliferation of CD4(+)CD25(-) T cells. On day 21, the expression of CXCR3 on Tregs and its ligand CXCL9 in hepatic tissue was upregulated, and levels of mRNA of transforming growth factor (TGF)-beta and IL-2, essential for Treg differentiation, in the liver were also increased. Suppression of AHI activity by prednisolone treatment decreased Treg accumulation in the liver. Accumulation of Tregs might occur through Treg recruitment mediated by CXCR3/CXCL9 interaction and expansion in the liver by upregulated TGF-beta and IL-2.
Saeki
Chisato
C
Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
Nakano
Masanori
M
Takahashi
Hiroki
H
Saito
Saburo
S
Homma
Sadamu
S
Tajiri
Hisao
H
Zeniya
Mikio
M
D000818:Animals; D049109:Cell Proliferation; D054370:Chemokine CXCL9 / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology*; D019693:Hepatitis, Autoimmune / Q000276:immunology*; D015151:Immunoblotting; D007150:Immunohistochemistry; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D054367:Receptors, CXCR3 / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology
D054370:Chemokine CXCL9; C485969:Cxcl9 protein, mouse; C515188:Cxcr3 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007376:Interleukin-2; D012333:RNA, Messenger; D054367:Receptors, CXCR3; D016212:Transforming Growth Factor beta