Ito Cells Are Liver-Resident Antigen-Presenting Cells for Activating T Cell Responses

Winau, Florian; Hegasy, Guido; Weiskirchen, Ralf; Weber, Stephan; Cassan, Cécile; Sieling, Peter A.; Modlin, Robert L.; Liblau, Roland; Gressner, A. M.; Kaufmann, Stefan H. E.

doi:10.1016/j.immuni.2006.11.011

Cited by 356 publications

(301 citation statements)

References 52 publications

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“…Transmigrating T cells might rapidly remigrate, receive suppressive signals upon transmigration, 43,44 or subsequently interact with tolerogenic Ito cells. 45 In this respect, endothelial cells from the liver sinusoids seem to possess a special feature in facilitating T cell balance and immune surveillance under homeostatic conditions and presumably even more strongly under inflammatory conditions. It is tempting to speculate that inhibition of chemokine presentation by LSEC might provide a future therapeutic approach to suppressing lymphocyte immigration to treat hepatic inflammation.…”

Section: Discussionmentioning

confidence: 99%

Enhanced T cell transmigration across the murine liver sinusoidal endothelium is mediated by transcytosis and surface presentation of chemokines

et al. 2008

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Transmigration through the liver endothelium is a prerequisite for the homeostatic balance of intrahepatic T cells and a key regulator of inflammatory processes within the liver. Extravasation into the liver parenchyma is regulated by the distinct expression patterns of adhesion molecules and chemokines and their receptors on the lymphocyte and endothelial cell surface. In the present study, we investigated whether liver sinusoidal endothelial cells ( H omeostatic extravasation into the liver parenchyma and transmigration of T cells into sites of inflammation under pathological conditions such as hepatitis and cholangitis are mediated by multiple steps involving activation and firm adhesion followed by egress. The process is closely regulated by the distinct expression patterns of adhesion molecules and chemokines and their receptors on the cell surface. 1,2 Within the liver, lymphocyte adhesion, a prerequisite for transmigration, occurs mainly within the sinusoidal circulation. Thus, T cell immigration into the liver is presumed to happen predominantly via the sinusoids. 3 Liver sinusoidal endothelial cells (LSEC) lining the sinusoids form a morphologically and functionally distinct endothelium that lacks a basement membrane, fails to form tight junctions, and displays fenestrae grouped to sieve plates. 4 In contrast to other tissues, selectins are not necessary for the initial adhesion of leukocytes to the liver microvasculature. The

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Section: Discussionmentioning

confidence: 99%

Enhanced T cell transmigration across the murine liver sinusoidal endothelium is mediated by transcytosis and surface presentation of chemokines

et al. 2008

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“…One third of liver cells are constituted by non-parenchymal cells (NPCs), which include liver sinusoidal endothelial cells (LSECs), Kupffer cells, biliary cells, stellate cells (Ito or fat-storing) cells and lymphocytes [74,75] . Resident APCs in the liver are Kupffer cells, LSEC [76] , Ito cells [77] and DCs [75] . Plasmacytoid B220 + CD11c + DCs as well as B220 -…”

Section: Hematogenous Dissemination Of Intestinal Antigensmentioning

confidence: 99%

Role of mucosal dendritic cells in inflammatory bowel disease

Niess

2008

WJG

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The gastrointestinal innate and adaptive immune system continuously faces the challenge of potent stimuli from the commensal microflora and food constituents. These local immune responses require a tight control, the outcome of which is in most cases the induction of tolerance. Local T cell immunity is an important compartment of the specific intestinal immune system. T cell reactivity is programmed during the initial stage of its activation by professional presenting cells. Mucosal dendritic cells (DCs) are assumed to play key roles in regulating immune responses in the antigenrich gastrointestinal environment. Mucosal DCs are a heterogeneous population that can either initiate (innate and adaptive) immune responses, or control intestinal inflammation and maintain tolerance. Defects in this regulation are supposed to lead to the two major forms of inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC). This review will discuss the emerging role of mucosal DCs in regulating intestinal inflammation and immune responses.

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“…41 In contrast, natural killer cells play an important role in clearing activated stellate cells, 42,43 an activity enhanced by gamma interferon and retinoic acid 44 and abrogated by ethanol. 45 Intriguingly, stellate cells also are antigen-presenting cells, 46 and may contribute to the liver's immunotolerant properties through T-cell suppression. 47 Finally, B lymphocytes, which comprise up to 50% of the total lymphocyte pool in liver, contribute to the fibrogenic milieu because mice lacking B cells (JH−/− animals) have attenuated fibrosis, apparently by more rapid ECM degradation after CCl 4 injury, implicating an unknown interaction with pathways of matrix degradation.…”

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confidence: 99%

Mechanisms of Hepatic Fibrogenesis

2008

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Substantial improvements in the treatment of chronic liver disease have accelerated interest in uncovering the mechanisms underlying hepatic fibrosis and its resolution. Activation of resident hepatic stellate cells into proliferative, contractile, and fibrogenic cells in liver injury remains a dominant theme driving the field. However, several new areas of rapid progress in the past 5-10 years also have taken root, including: (1) identification of different fibrogenic populations apart from resident stellate cells, for example, portal fibroblasts, fibrocytes, and bone-marrow-derived cells, as well as cells derived from epithelial mesenchymal transition; (2) emergence of stellate cells as finely regulated determinants of hepatic inflammation and immunity; (3) elucidation of multiple pathways controlling gene expression during stellate cell activation including transcriptional, posttranscriptional, and epigenetic mechanisms; (4) recognition of disease-specific pathways of fibrogenesis; (5) re-emergence of hepatic macrophages as determinants of matrix degradation in fibrosis resolution and the importance of matrix cross-linking and scar maturation in determining reversibility; and (6) hints that hepatic stellate cells may contribute to hepatic stem cell behavior, cancer, and regeneration. Clinical and translational implications of these advances have become clear, and have begun to impact significantly on the management and outlook of patients with chronic liver disease.The field of hepatic fibrosis is flourishing thanks to continued experimental advances complemented by exciting progress in the treatment of chronic liver disease. 1 Control of chronic hepatitis B and C by antiviral therapies has established that advanced fibrosis can regress in association with improved clinical outcomes, 2-4 thereby intensifying enthusiasm to uncover the mechanistic basis for hepatic fibrogenesis and its attenuation. At the same time, simple paradigms defining the cellular sources of extracellular matrix (ECM), and the roles of cytokines and paracrine interactions among resident liver cells and inflammatory cells have yielded a more nuanced understanding of how the liver responds to injury. These advances have had a collateral benefit towards understanding fibrosis in other organs, particularly the pancreas. 5 Thus, a review of the mechanisms underlying hepatic fibrosis is not only timely, but is more clinically relevant than ever. This article focuses on recent advances in the field, building on established principles from earlier reviews 6,7 while weaving in their clinical relevance, but also emphasizing the molecular subtleties that have emerged through continued progress in the field. General PrinciplesFibrosis, or scarring of the liver, is a wound-healing response that engages a range of cell types and mediators to encapsulate injury. Although even acute injury will activate mechanisms of fibrogenesis, the sustained signals associated with chronic liver disease caused by infection, Cirrhosis, the most advanced stage ...

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Ito Cells Are Liver-Resident Antigen-Presenting Cells for Activating T Cell Responses

Cited by 356 publications

References 52 publications

Enhanced T cell transmigration across the murine liver sinusoidal endothelium is mediated by transcytosis and surface presentation of chemokines

Enhanced T cell transmigration across the murine liver sinusoidal endothelium is mediated by transcytosis and surface presentation of chemokines

Role of mucosal dendritic cells in inflammatory bowel disease

Mechanisms of Hepatic Fibrogenesis

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