Original Contribution
The American Journal of Gastroenterology (2007) 102, 302–312; doi:10.1111/j.1572-0241.2006.00948.x
Expression of PD-1, PD-L1, and PD-L2 in the Liver in Autoimmune Liver Diseases
Norikazu Mataki1, Kentaro Kikuchi2, Toshihiro Kawai1, Masaaki Higashiyama1, Yoshikiyo Okada1, Chie Kurihara1, Ryota Hokari1, Atsushi Kawaguchi3, Shigeaki Nagao3, Toshiro Kondo4, Kazuro Itoh1, Hiroshi Miyakawa2 and Soichiro Miura3
- 1Department of Internal Medicine, National Defense Medical College, Saitama, Japan
- 2Fourth Department of Internal Medicine, Teikyo University School of Medicine, Kawasaki, Japan
- 3Department of Endoscopic and Photodynamics, National Defense Medical College, Saitama, Japan
- 4Department of Internal Medicine, Japan Self Defense Forces Kumamoto Hospital, Kumamoto, Japan
Correspondence: Norikazu Mataki, Second Department of Internal Medicine, National Defense Medical College, Namiki 3-2 Tokorozawa, Saitama 359-8513, Japan
Received 1 February 2006; Accepted 5 September 2006.
Abstract
OBJECTIVES:
PD-L1 (also B7-H1) and PD-L2 (also B7-DC) are ligands for programmed death-1 (PD-1), which is a member of the CD28/B7 superfamily of costimulatory molecules and plays an inhibitory role on the periphery. Impaired regulation of this system may cause disruption to self-tolerance leading to autoimmunity; however, the role of these molecules in the liver is unknown. Therefore, we examined the expression of PD-1, PD-L1, and PD-L2 in the liver in autoimmune liver diseases.
METHODS:
We examined the liver expression of these molecules in autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) with no previous medical treatment using immunohistochemical staining and real-time PCR, and compared with chronic hepatitis type C (CHC) as a control.
RESULTS:
Although PD-1, PD-L1, and PD-L2 were expressed in the liver in AIH, PBC, as well as CHC, the expressions were relatively lower in PBC. In AIH, despite more severe inflammation than in CHC, the expression of these molecules was not greater than in CHC, and when compared with the relative expression of PD-L1, PD-L2 was lower in AIH. PD-L1 and PD-L2 expressions were well correlated with the level of IFN-
; however, relatively decreased induction for PD-L1 and PD-L2 by IFN- was observed in AIH or PBC than in CHC.
CONCLUSION:
Modulation of PD-1/PD-L1 and PD-L2 systems may play a role in the development of autoimmune liver diseases.
