A multifaceted imbalance of T cells with regulatory function characterizes type 1 autoimmune hepatitis

Ferri, Silvia; Longhi, Maria Serena; Molo, Chiara De; Lalanne, Claudine; Muratori, Paolo; Granito, Alessandro; Hussain, Munther J.; Ma, Yuanfang; Lenzi, Marco; Mieli‐Vergani, Giorgina; Bianchi, Francesco; Vergani, Diego

doi:10.1002/hep.23792

Cited by 177 publications

(137 citation statements)

References 45 publications

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“…and CD8+ Tregs have been demonstrated by a number of studies on autoimmune diseases (22)(23)(24), transplantation (25) and inflammatory diseases (26). ACAID has also been shown to significantly suppress the induction of experimental uveoretinitis (27).…”

Section: Splenic Cd8+ T Cells From Balble Mice Injected With Cii-spmentioning

confidence: 99%

Thein vitro-Inductionof Type II Collagen-Specific Immune Tolerance in BALB/C Mice

Farooq

2013

Eur J Inflamm

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Type II collagen (CII) protein is the main component of hyaline cartilage. The clinical importance of CII in arthritis, aging, and osteoarthritis is significant, but its ability to induce specific immune tolerance has not been extensively studied previously. We have recently proven that CII is capable of inducing Anterior Chamber Associated Immune Deviation (ACAID) when injected into the eye. Here, we hypothesized that ACAID-mediated tolerance could be induced in Balb/c mice that receive an intravenous administration of CII-induced in vitro-generated ocular-like antigen-presenting cells (APCs) or T regulatory cells (Tregs), Delayed hypersensitivity (DTH) assays were used to examine this hypothesis. In mice injected with CII-specific ACAID APCs, the specific regulatory activities resided in the spleen cells, splenic T cells, and ACAID CD8+ T cells, as proven by local adoptive transfer (LAT) assays. Conversely, there was a lack of regulatory activity in the CD4+ CD25+ T cell compartment of the recipient mice. Thus, ACAID CD8+ Tregs generated in vitro could be directly responsible for the expression of CII-driven ACAID-mediated tolerance and could be used as potential therapeutic tools in the treatment of CII-associated autoimmune diseases.The eye is vulnerable to severe inflammatory immune responses that could cause serious damage. Thus, regulatory mechanisms are in place to protect against intra-ocular inflammation. Anterior chamber-associated immune deviation (ACAID) is one such mechanism whereby the antigenic entry into the AC induces potent antigen-specific immune tolerance that is not only localized in the eye but also extends to the periphery. In order to obtain this potent antigen-specific peripheral immune tolerance, ACAID involves intricate multicellular communications between the eye-derived F4/80+ antigen presenting cells (APCs), splenic T cells, marginal zone B cells, NKT cells, and yo T cells (l). ACAID is characterized by the negative regulation of systemic Th 1 responses and of delayed type hypersensitivity (DTH) responses (2). This is achieved through professional APCs that induce the generation of afferent and efferent T regulatory cells (Tregs) (3), which could potentially be used to curb T-helper cell responses in autoimmune diseases. Professional APCs can be immunogenic or tolerogenic depending on the involvement of unique cytokines that impact their maturation and activation, such as the immunosuppressive cytokines IL-I 0 and TGF-~that push towards the tolerogenic type (4, 5). The in vitro culture of F4/80+ macrophages with antigens in the presence ofTGF-~2 could lead to the

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Section: Splenic Cd8+ T Cells From Balble Mice Injected With Cii-spmentioning

confidence: 99%

Thein vitro-Inductionof Type II Collagen-Specific Immune Tolerance in BALB/C Mice

Farooq

2013

Eur J Inflamm

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“…[77] Cytokines and autoimmune hepatitis Autoimmune hepatitis (AIH) is an inflammatory liver disorder, characterized by female preponderance, hypergammaglobulinaemia and interface hepatitis on histology. AIH is associated with impairment of regulatory T-cells, [78] a lymphocyte subset key in maintaining immune-tolerance to autoantigens. [79] Limited data are available for the participation of cytokines in the development of AIH.…”

Section: Structural Organization Of the Liver And Cytokines Potentialmentioning

confidence: 99%

Physiological potential of cytokines and liver damages

Mannaa¹,

Abdel-Wahhab²

2016

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Cytokines are soluble extracellular small molecular weight protein or peptide. They are produced by virtually every nucleated cell type in response to injurious stimuli to control body metabolism, infection, inflammation and tissue or neuronal damage; therefore acting as messengers between tissues and the immune system; and participating in many physiological processes through their either anti-inflammatory or pro-inflammatory characteristics. Many cytokines have multiple cellular sources and targets, as well as many natural inducers and inhibitors. In pathophysiological conditions and during the early phase of chronic liver diseases, agent like virus, bacteria, parasites, ethanol, or toxins, induce secretion of cytokines at high levels. The presence of cytokine antagonists and soluble cytokine receptors, often released in concert with their respective cytokine agonist, presents additional complexity to interpretation.

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“…Among them, regulatory T cells are particularly important because they participate in the maintenance of immune self-tolerance and homeostasis (25). Moreover, different studies have found a relationship between the impaired number and function of Treg cells and AIH (26,27). It has also been shown that restoration of Treg cell function in subjects with AIH is paralleled by an increase in the expression of Th1/Th2/Th17 transcription factors (28).…”

Section: Controlsmentioning

confidence: 99%

Role of Th1/Th2 cells and related cytokines in autoimmune hepatitis

Behfarjam

Sanati²,

Moghaddam³

et al. 2017

Turk J Gastroenterol

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Background/Aims: Dysregulation of T cell response is thought to play an important role in the immunopathogenesis of autoimmune hepatitis. However, no consensus has yet been reached regarding the implications of a distinct T cell subset in the pathogenesis of this progressive liver disease. Therefore, T-bet and GATA-3 expression was examined in patients with autoimmune hepatitis (AIH) and in healthy controls. Moreover, the profile of Th1 (IFN-γ) and Th2 (IL-4) cytokine gene expression was analyzed. Materials and Methods: Levels of mRNA transcripts were measured in peripheral blood mononuclear cells (PBMCs) using a two-step reverse transcription quantitative real-time polymerase chain reaction with SYBR Green. Results: T-bet and IFN-γ mRNA expression was significantly higher in AIH patients compared to healthy controls (p<0.05), whereas no differences were observed for either GATA-3 or IL-4 mRNA expression (p>0.05). Conclusion: Alterations in the Th1/Th2 cell balance may be responsible for both disease progression and the resulting complications.

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A multifaceted imbalance of T cells with regulatory function characterizes type 1 autoimmune hepatitis

Cited by 177 publications

References 45 publications

Thein vitro-Inductionof Type II Collagen-Specific Immune Tolerance in BALB/C Mice

Thein vitro-Inductionof Type II Collagen-Specific Immune Tolerance in BALB/C Mice

Physiological potential of cytokines and liver damages

Role of Th1/Th2 cells and related cytokines in autoimmune hepatitis

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