CXCR3 axis in patients with primary biliary cirrhosis: a possible novel mechanism of the effect of ursodeoxycholic acid

Summary The CXC chemokines, monokine induced by interferon (IFN)‐gamma (MIG) ( CXCL9 ), IFN‐gamma‐induced protein 10 ( IP ‐10) ( CXCL10 ) and IFN‐inducible T cell alpha chemoattractant (I ‐ TAC) ( CXCL11 ), are known to attract CXCR3 ‐ ( CXCR3A and CXCR3B ) T lymphocytes. We investigated M IG, IP ‐10 and I ‐ TAC mRNAs expression by semi‐quantitative multiplex reverse transcription–polymerase chain reaction ( RT–PCR) in liver biopsies obtained from patients with a first diagnosis of primary biliary cirrhosis [( PBC)  = 20] compared to patients with normal liver biopsy [normal controls ( NCs)  = 20]. Chemokine production was assessed by enzyme‐linked immunosorbent assay ( ELISA) in serum. Measurements were repeated 6 months after ursodeoxycholic acid ( UDCA) treatment in PBC patients. CXCR3A and CXCR3B mRNAs expression was examined in immunomagnetically sorted CD3 + peripheral blood lymphocytes ( PBL ) pre‐ and post‐treatment by RT–PCR . Flow cytometry was used to evaluate the expression of CXCR3 + PBLs of NCs and PBC patients. A marked mRNA expression of MIG and IP‐10 was found in PBC patients. I‐ TAC mRNA was not detected. In serum of PBC patients there was a significant increase of MIG and IP ‐10 compared to NCs . Interestingly, there was a significant reduction of these proteins in patients' serum after UDCA treatment. I ‐ TAC was not statistically different between groups. CXCR3A mRNA expression was found in PBLs from PBC patients as well as in NCs . CXCR3B mRNA was expressed in four of 20 (19%) NCs and 20 of 20 PBC patients. Flow cytometry revealed a significantly lower CXCR3 expression in NCs (13·5%) than in PBC (37·2%), which was reduced (28·1%, P  < 0·01) after UDCA administration. These data suggest a possible role for CXCR3 ‐binding chemokines and their receptor in the aetiopathogenetic recruitment of lymphocytes in PBC and a new mechanism of action for UDCA .