Phenotypic alterations of regulatory T cells in autoimmune hepatitis: Causal or associated with treatment and remission?

Sebode, Marcial; Peiseler, Moritz; Weiler‐Normann, Christina; Schramm, Christoph; Lohse, Ansgar W.; Herkel, Johannes

doi:10.1002/hep.27301

Cited by 5 publications

(5 citation statements)

References 6 publications

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“…Magnetically isolated CD4 pos CD25 pos CD127 neg Tregs from AIH patients were also less able to suppress proliferation than from HS [57], although this defect was not observed in FACS isolated CD4 pos CD25 high CD127 neg cells [177]. The discrepant results reported in AIH are likely to derive from differences in methodology, patient demography, disease activity and type of treatment [182,183].…”

Section: Regulatory T Cells In Autoimmune Liver Diseasementioning

confidence: 99%

Regulatory T-cells in autoimmune diseases: Challenges, controversies and—yet—unanswered questions

Grant

Liberal

Mieli‐Vergani

et al. 2015

Autoimmunity Reviews

247

158

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Regulatory T cells (Tregs) are central to the maintenance of self-tolerance and tissue homeostasis. Markers commonly used to define human Tregs in the research setting include high expression of CD25, FOXP3 positivity and low expression/negativity for CD127. Many other markers have been proposed, but none unequivocally identifies bona fide Tregs. Tregs are equipped with an array of mechanisms of suppression, including the modulation of antigen presenting cell maturation and function, the killing of target cells, the disruption of metabolic pathways and the production of anti-inflammatory cytokines. Treg impairment has been reported in a number of human autoimmune conditions and includes Treg numerical and functional defects and conversion into effector cells in response to inflammation. In addition to intrinsic Treg impairment, resistance of effector T cells to Treg control has been described. Discrepancies in the literature are common, reflecting differences in the choice of study participants and the technical challenges associated with investigating this cell population. Studies differ in terms of the methodology used to define and isolate putative regulatory cells and to assess their suppressive function. In this review we outline studies describing Treg frequency and suppressive function in systemic and organ specific autoimmune diseases, with a specific focus on the challenges faced when investigating Tregs in these conditions.

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Section: Regulatory T Cells In Autoimmune Liver Diseasementioning

confidence: 99%

Regulatory T-cells in autoimmune diseases: Challenges, controversies and—yet—unanswered questions

Grant

Liberal

Mieli‐Vergani

et al. 2015

Autoimmunity Reviews

247

158

View full text Add to dashboard Cite

show abstract

“…Tregs can exhibit therapeutic potential against immunemediated liver injury and are actively engaged in the negative control of a variety of pathological immune responses in the liver, including hepatic ischemia-reperfusion injury (Lu et al, 2009), chronic hepatitis B virus/hepatitis C virus infection Losikoff et al, 2015), autoimmune hepatitis (Sebode et al, 2015) and hepatocellular carcinoma (Guo et al, 2014). The immunosuppressive cytokine IL-10 and Treg are crucial for tolerance induction in ConA hepatitis (Erhardt et al, 2007).…”

Section: T-helper 17/regulatory T Cells In Liver Injurymentioning

confidence: 99%

T‐helper cell‐mediated factors in drug‐induced liver injury

Wang

Zhang

Jiang

2015

J of Applied Toxicology

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Drug-induced liver injury (DILI) leads to a large burden on the healthcare system due to its potential morbidity and mortality. The key for predicting and preventing DILI is to understand the underlying mechanisms. Hepatic inflammation is one of the most common features of DILI. The inflammation can be attributed to the innate immune response. The adaptive immune system is also affected by the innate immune response resulting in liver damage. T-helper cells are important regulators of acquired immunity. T-helper cell-mediated immune responses play pivotal roles in the pathogenesis of a variety of liver disorders. This review summarizes recent advances in the T-helper cell-mediated factors in DILI and potential mechanisms, which may lead to a better understanding of DILI.

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“…The role of Treg for AIH has for some years been controversial . However, in recent years discrepant findings from different groups could largely be explained by differences in methodology and, even more so, be due to different patient groups being investigated (children vs adults, pure AIH vs mixture of AIH and AIH/PSC, active untreated, active treated and inactive treated disease).…”

Section: Pathogenesis Of Autoimmune Hepatitismentioning

confidence: 99%

“…This is a matter of debate since it seems that no "standard control" for studies into AIH pathogenesis exists, except The role of Treg for AIH has for some years been controversial. [13][14][15][16][17][18] However, in recent years discrepant findings from different groups could largely be explained by differences in methodology and, even more so, be due to different patient groups being investigated (children vs adults, pure AIH vs mixture of AIH and AIH/PSC, active untreated, active treated and inactive treated disease). Altogether it is clear that in active AIH, Treg fail to control or suppress intrahepatic inflammation sufficiently to prevent the disease.…”

Section: Key Pointsmentioning

confidence: 99%

Autoimmune hepatitis: From current knowledge and clinical practice to future research agenda

Sebode

Hartl

Vergani

et al. 2017

Liver International

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Autoimmune hepatitis is a chronic inflammatory liver disease. Unknown triggers lead to a mainly T cell-mediated immune response targeting the liver, the main auto-antigen of which has not been identified yet. The diagnosis of autoimmune hepatitis is based on the elevation of immunoglobulin G/hypergammaglobulinemia, detection of characteristic autoantibodies as well as a typical pattern on liver histology. Exclusion of other causes of hepatitis and response to immunosuppressive treatment support the diagnosis of autoimmune hepatitis. The mainstay of autoimmune hepatitis treatment has, from its first description to the current time, consisted of predniso(lo)ne to induce remission, in combination with azathioprine, which is used to maintain it. Nonetheless, side effects and non-response with ongoing inflammation despite standard therapy demand treatment alternatives. Only through a better understanding of the pathogenesis of autoimmune hepatitis can a more selective and effective treatment be offered to patients in the future. Until this goal is reached, improvement of diagnostic approaches and optimization of current therapy rank highest on the research agenda for autoimmune hepatitis.

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Phenotypic alterations of regulatory T cells in autoimmune hepatitis: Causal or associated with treatment and remission?

Cited by 5 publications

References 6 publications

Regulatory T-cells in autoimmune diseases: Challenges, controversies and—yet—unanswered questions

Regulatory T-cells in autoimmune diseases: Challenges, controversies and—yet—unanswered questions

T‐helper cell‐mediated factors in drug‐induced liver injury

Autoimmune hepatitis: From current knowledge and clinical practice to future research agenda

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