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

Manousou, Pinelopi; Kolios, George; Drygiannakis, Ioannis; Koulentaki, Mairi; Pyrovolaki, Katerina; Voumvouraki, Argyro; Notas, George; Bourikas, Leonidas A.; Papadaki, Helen Α.

doi:10.1111/cei.12032

Cited by 36 publications

(37 citation statements)

References 33 publications

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“…CXCL9 (monokine induced by interferon-c [MIG]) and CXCL10 (interferon-c-inducible protein 10 [IP-10]) are increased in autoimmune hepatitis, and they have been associated with disease severity and progression [215,[221][222][223] (Table 3). The cognate receptor of CXCL9 is CXCR3 [224], and Th1 and Th17 lymphocytes bearing this receptor are attracted to the monocyte-derived dendritic cells within the liver that produce CXCL9 [225]. CXCL10 is secreted by monocytes, neutrophils, endothelial cells, fibroblasts, dendritic cells, CD4 ?…”

Section: Insights Into the Chemokine Milieu Of Autoimmune Hepatitismentioning

confidence: 99%

Transitioning from Idiopathic to Explainable Autoimmune Hepatitis

Czaja

2015

Dig Dis Sci

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Autoimmune hepatitis lacks an identifiable cause, and its diagnosis requires the exclusion of etiologically defined diseases that resemble it. Insights into its pathogenesis are moving autoimmune hepatitis from an idiopathic to explainable disease, and the goal of this review is to describe the insights that are hastening this transition. Two types of autoimmune hepatitis are justified by serological markers, but they also have distinctive genetic associations (DRB1 and DQB1 genes) and autoantigens. DRB1 alleles are the principal susceptibility factors in white adults, and a six amino acid sequence encoded in the antigen-binding groove of class II molecules of the major histocompatibility complex can influence the selection of autoantigens. Polymorphisms, including variants of SH2B3 and CARD10 genes, may affect immune reactivity and disease severity. The cytochrome mono-oxygenase, CYP2D6, is the autoantigen associated with type 2 autoimmune hepatitis, and it shares homologies with multiple viruses that might promote self-intolerance by molecular mimicry. Chemokines, especially CXCL9 and CXCL10, orchestrate the migration of effector cells to sites of injury and are associated with disease severity. Cells of the innate and adaptive immune responses promote tissue damage, and possible deficiencies in the number and function of regulatory T cells may facilitate the injurious process. Receptor-mediated apoptosis is the principal mechanism of hepatocyte loss, and cell-mediated and antibody-dependent mechanisms of cytotoxicity also contribute. Insights that explain autoimmune hepatitis will allow triggering exogenous antigens to be characterized, risk management to be improved, prognostic indices to be refined, and site-specific therapeutic interventions to emerge.

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Section: Insights Into the Chemokine Milieu Of Autoimmune Hepatitismentioning

confidence: 99%

Transitioning from Idiopathic to Explainable Autoimmune Hepatitis

Czaja

2015

Dig Dis Sci

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“…These processes themselves are at least partly initiated and modulated by chemokines [3,4]. In particular, CXCR3 ligands, especially CXCL9, are increased during liver diseases [5][6][7][8][9][10][11][12] and are functionally linked to hepatic injury, inflammation, fibrosis, [8][9][10][12][13][14][15][16][17][18], angiogenesis [6] and complications of cirrhosis [19]. Liver resident cells, such as hepatocytes, Kupffer cells and hepatic stellate cells were found to represent a major source of CXCR3 ligands in the liver [20][21][22][23][24][25].…”

Section: Introductionmentioning

confidence: 99%

CXCL9 is a prognostic marker in patients with liver cirrhosis receiving transjugular intrahepatic portosystemic shunt

Berres¹,

Asmacher²,

Lehmann³

et al. 2015

Journal of Hepatology

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“…Moreover we demonstrated using flow cytometry a significantly lower CXCR3 expression in normal controls (13.5%) compared to PBC (37.2%), which was decreased (28.1%, P < 0.01) after UDCA treatment, a finding that might indicate a new additional mechanism of action for UDCA [134] .…”

Section: Mode Of Action Of Udcamentioning

confidence: 63%

“…However the CXCR3B variant mRNA was expressed in 4/20 (19%) normal controls and all 20 PBC patients. These data suggest a possible pathogenetic implication of MIG and IP-10 chemokines and their receptor in the pathogenesis of PBC [134] . Recent papers demonstrated that these chemokines and their receptors are also involved in the hepatic recruitment of Tregs and the proinflammatory Th17 and Tc17+ lymphocytes [135,136] .…”

Section: Chemokines In Pbcmentioning

confidence: 67%

Primary biliary cirrhosis: From bench to bedside

Notas

2015

WJGPT

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Primary biliary cirrhosis (PBC) is a chronic nonsuppurative destructive intrahepatic cholangitis leading to cirrhosis after a protractive non cirrhotic stage. The etiology and pathogenesis are largely unknown and autoimmne mechanisms have been implicated to explain the pathological lesions. Many epitopes and autoantigens have been reported as crucial in the pathophysiology of the disease and T and B cells abnormalities have been described, the exact pathways leading to the destruction of small intrahepatic ductules are mostly speculative. In this review we examined the various epidemiologal and geoepidemiological data as well as the complex pathogenetic aspects of this disease, focusing on recent in vivo and in vitro studies in this field. Initiation and progression of PBC is believed to be a multifactorial process with strong infuences from the patient's genetic background and by various environmental factors. The role of innate and adaptive immunity, including cytokines, chemokines, macrophages and the involvement of apoptosis and reactive oxygen species are outlined in detailed. The current pathogenetic aspects are presented and a novel pathogenetic theory unifying the accumulated clinical information with in vitro and in vivo data is formulated.A review of clinical manifestations and immunological and pathological diagnosis was presented. Treatment modalities, including the multiple mechanisms of action of ursodeoxycholate were finally discussed. Core tip: Primary biliary cirrhosis (PBC) is a chronic nonsuppurative destructive intrahepatic cholangitis leading to cirrhosis of largely unknown pathophysiology. We examined the epidemiological and geoepidemiological data as well as the pathogenetic aspects of PBC. A novel pathogenetic theory unifying the accumulated clinical information with in vitro and in vivo data is formulated.

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

Cited by 36 publications

References 33 publications

Transitioning from Idiopathic to Explainable Autoimmune Hepatitis

Transitioning from Idiopathic to Explainable Autoimmune Hepatitis

CXCL9 is a prognostic marker in patients with liver cirrhosis receiving transjugular intrahepatic portosystemic shunt

Primary biliary cirrhosis: From bench to bedside

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