<i>Foxp3</i>Expression in Liver Correlates with the Degree but Not the Cause of Inflammation

Speletas, Matthaios; Argentou, Nikoletta; Germanidis, Georgios; Vasiliadis, Themistoklis; Mantzoukis, Konstantinos; Patsiaoura, Kalliopi; Nikolaidis, Pavlos; Karanikas, Vaios; Ritis, Konstantinos; Germenis, Anastasios E.

doi:10.1155/2011/827565

Cited by 41 publications

(48 citation statements)

References 51 publications

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“…This observation is also in accordance with previous reports [24,[50][51][52]. Moreover, although CD8 + /Foxp3 + cells have been described in CHC biopsies [31,53],they were under-represented in our studied series, as in other reports [51,52].…”

Section: Mann-whitney U-test and Unpaired T-testsupporting

confidence: 94%

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Distinctive intrahepatic characteristics of paediatric and adult pathogenesis of chronic hepatitis C infection

Valva

Gismondi

Casciato

et al. 2014

Clinical Microbiology and Infection

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Mechanisms leading to liver damage in chronic hepatitis C (CHC) are being discussed, but both the immune system and the virus are involved. The aim of this study was to evaluate intrahepatic viral infection, apoptosis and portal and periportal/interface infiltrate in paediatric and adult patients to elucidate the pathogenesis of chronic hepatitis C. HCV-infected, activated caspase-3(+) and TUNEL(+) hepatocytes, as well as total, CD4(+), CD8(+), Foxp3(+) and CD20(+) lymphocytes infiltrating portal and periportal/interface tracts were evaluated in 27 paediatric and 32 adult liver samples by immunohistochemistry or immunofluorescence. The number of infected hepatocytes was higher in paediatric than in adult samples (p 0.0078). In children, they correlated with apoptotic hepatocytes (activated caspase-3(+) r = 0.74, p < 0.0001; TUNEL(+) r = 0.606, p 0.0017). Also, infected (p = 0.026) and apoptotic hepatocytes (p = 0.03) were associated with the severity of fibrosis. In adults, activated caspase-3(+) cell count was increased in severe hepatitis (p = 0.009). Total, CD4(+), CD8(+) and Foxp3(+) lymphocyte count was higher in adult samples (p < 0.05). Paediatric CD8(+) cells correlated with infected (r = 0.495, p 0.04) and TUNEL(+) hepatocytes (r = 0.474, p = 0.047), while adult ones correlated with activated caspase-3(+) hepatocytes (r = 0.387, p 0.04). In adults, CD8(+) was associated with hepatitis severity (p < 0.0001) and correlated with inflammatory activity (CD8(+) r = 0.639, p 0.0003). HCV, apoptosis and immune response proved to be involved in CHC pathogenesis of both paediatric and adult patients. However, liver injury in paediatric CHC would be largely associated with a viral cytopathic effect mediated by apoptosis, while in adults it would be mainly associated with an exacerbated immune response.

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Section: Mann-whitney U-test and Unpaired T-testsupporting

confidence: 94%

“…Accumulating evidence indicates that patients with chronic viral hepatitis display an increased number of Treg cells in peripheral blood or liver; however, the increment of Treg cells in CHC and their role in liver damage development is still a matter of debate [21][22][23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

Distinctive intrahepatic characteristics of paediatric and adult pathogenesis of chronic hepatitis C infection

Valva

Gismondi

Casciato

et al. 2014

Clinical Microbiology and Infection

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“…T regs secrete anti-inflammatory signals, inhibit macrophage migration, and induce noninflammatory M2-like macrophage differentiation (35). In addition, defects in T reg function are considered to play a role not only in autoimmune diseases, such as autoimmune hepatitis (36), but also in other causes of hepatic inflammation (37,38). In agreement with an anti-inflammatory property of lyso-PCs, we detected strong negative relationships of total lyso-PCs and lyso-PC C16:0 with hs-CRP levels in our subjects with NAFL.…”

Section: Discussionmentioning

confidence: 99%

Circulating Lysophosphatidylcholines Are Markers of a Metabolically Benign Nonalcoholic Fatty Liver

et al. 2013

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OBJECTIVENonalcoholic fatty liver (NAFL) is thought to contribute to insulin resistance and its metabolic complications. However, some individuals with NAFL remain insulin sensitive. Mechanisms involved in the susceptibility to develop insulin resistance in humans with NAFL are largely unknown. We investigated circulating markers and mechanisms of a metabolically benign and malignant NAFL by applying a metabolomic approach.RESEARCH DESIGN AND METHODSA total of 265 metabolites were analyzed before and after a 9-month lifestyle intervention in plasma from 20 insulin-sensitive and 20 insulin-resistant subjects with NAFL. The relevant plasma metabolites were then tested for relationships with insulin sensitivity in 17 subjects without NAFL and in plasma from 29 subjects with liver tissue samples.RESULTSThe best separation of the insulin-sensitive from the insulin-resistant NAFL group was achieved by a metabolite pattern including the branched-chain amino acids leucine and isoleucine, ornithine, the acylcarnitines C3:0-, C16:0-, and C18:0-carnitine, and lysophosphatidylcholine (lyso-PC) C16:0 (area under the ROC curve, 0.77 [P = 0.00023] at baseline and 0.80 [P = 0.000019] at follow-up). Among the individual metabolites, predominantly higher levels of lyso-PC C16:0, both at baseline (P = 0.0039) and at follow-up (P = 0.001), were found in the insulin-sensitive compared with the insulin-resistant subjects. In the non-NAFL groups, no differences in lyso-PC C16:0 levels were found between the insulin-sensitive and insulin-resistant subjects, and these relationships were replicated in plasma from subjects with liver tissue samples.CONCLUSIONSFrom a plasma metabolomic pattern, particularly lyso-PCs are able to separate metabolically benign from malignant NAFL in humans and may highlight important pathways in the pathogenesis of fatty liver–induced insulin resistance.

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“…Instead, peripheral and intrahepatic Treg frequency correlated with disease activity. This is further supported by a report which showed that Treg frequency is generally elevated in inflamed livers irrespective of its cause [32]. If there is not a global defect of Treg numbers in AIH, the question rises why the attracted Treg are not able to suppress hepatic inflammation?…”

Section: Regulatory T Cells In Aihmentioning

confidence: 65%

Future Perspective: Immunomodulatory Therapy for Autoimmune Hepatitis

Sebode

Lohse²

2014

Dig Dis

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In the last two decades, more and more light has been shed on the immunologic pathogenesis of autoimmune liver diseases, notably autoimmune hepatitis (AIH). An immunologic dysbalance with proinflammatory immune responses dominating over hepatic tolerance seems to be part of AIH pathogenesis. In detail, an impairment of regulatory T cells (Treg) is suspected. If this holds true and reduced Treg numbers or their function are pathogenic for AIH, this offers the option of cellular or immunomodulatory therapy. However, the exact immunological role of Treg in AIH still needs to be clarified before cellular therapy is promising for patients.

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Foxp3Expression in Liver Correlates with the Degree but Not the Cause of Inflammation

Cited by 41 publications

References 51 publications

Distinctive intrahepatic characteristics of paediatric and adult pathogenesis of chronic hepatitis C infection

Distinctive intrahepatic characteristics of paediatric and adult pathogenesis of chronic hepatitis C infection

Circulating Lysophosphatidylcholines Are Markers of a Metabolically Benign Nonalcoholic Fatty Liver

Future Perspective: Immunomodulatory Therapy for Autoimmune Hepatitis

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