Expression of PD-1, PD-L1, and PD-L2 in the Liver... : American Journal of Gastroenterology (original) (raw)

ORIGINAL CONTRIBUTION: LIVER AND BILIARY TRACT

Expression of PD-1, PD-L1, and PD-L2 in the Liver in Autoimmune Liver Diseases

Norikazu Mataki
Kentaro Kikuchi
Toshihiro Kawai
Masaaki Higashiyama
Yoshikiyo Okada
Chie Kurihara
Ryota Hokari
Atsushi Kawaguchi
Shigeaki Nagao
Toshiro Kondo
Kazuro Itoh
Hiroshi Miyakawa
Soichiro Miura

American Journal of Gastroenterology

102

(

)

302

312

February 2007

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-γ; however, relatively decreased induction for PD-L1 and PD-L2 by IFN-γ 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.