Expression of PD-1, PD-L1, and PD-L2 in the liver in autoimmune liver diseases.
OBJECTIVE
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-gamma; however, relatively decreased induction for PD-L1 and PD-L2 by IFN-gamma was observed in AIH or PBC than in CHC.


CONCLUSIONS
Modulation of PD-1/PD-L1 and PD-L2 systems may play a role in the development of autoimmune liver diseases.
Mataki
Norikazu
N
Department of Internal Medicine, National Defense Medical College, Saitama, Japan.
Kikuchi
Kentaro
K
Kawai
Toshihiro
T
Higashiyama
Masaaki
M
Okada
Yoshikiyo
Y
Kurihara
Chie
C
Hokari
Ryota
R
Kawaguchi
Atsushi
A
Nagao
Shigeaki
S
Kondo
Toshiro
T
Itoh
Kazuro
K
Miyakawa
Hiroshi
H
Miura
Soichiro
S
D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics*; D060890:B7-H1 Antigen; D015415:Biomarkers / Q000378:metabolism; D001707:Biopsy, Needle; D003937:Diagnosis, Differential; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D019693:Hepatitis, Autoimmune / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D060890:B7-H1 Antigen; D015415:Biomarkers; C423236:CD274 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C105992:PDCD1 protein, human; C556977:PDCD1LG2 protein, human; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; D012333:RNA, Messenger