Immune Cell Trafficking to the Liver

Chaudhry, Sulemon; Emond, Jean C.; Griesemer, Adam

doi:10.1097/tp.0000000000002690

Cited by 33 publications

(25 citation statements)

References 259 publications

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“…The liver is enriched with immune cells and cytokines that create a tolerogenic microenvironment [236][237][238][239][240][241][242]. These cells produce anti-inflammatory cytokines (IL-10, TGFβ) or manifest weak or oppositional immune properties that reflect diverse inputs from hepatocytes, sinusoidal endothelial cells, and hepatic stellate cells [238].…”

Section: Overviewmentioning

confidence: 99%

Exploring the Pathogenic Role and Therapeutic Implications of Interleukin 2 in Autoimmune Hepatitis

Czaja

2020

Dig Dis Sci

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Interleukin 2 is essential for the expansion of regulatory T cells, and low-dose recombinant interleukin 2 has improved the clinical manifestations of diverse autoimmune diseases in preliminary studies. The goals of this review are to describe the actions of interleukin 2 and its receptor, present preliminary experiences with low-dose interleukin 2 in the treatment of diverse autoimmune diseases, and evaluate its potential as a therapeutic intervention in autoimmune hepatitis. English abstracts were identified in PubMed by multiple search terms. Full-length articles were selected for review, and secondary and tertiary bibliographies were developed. Interleukin 2 is critical for the thymic selection, peripheral expansion, induction, and survival of regulatory T cells, and it is also a growth factor for activated T cells and natural killer cells. Interleukin 2 activates the signal transducer and activator of transcription 5 after binding with its trimeric receptor on regulatory T cells. Immune suppressor activity is increased; anti-inflammatory interleukin 10 is released; pro-inflammatory interferon-gamma is inhibited; and activation-induced apoptosis of CD8 + T cells is upregulated. Preliminary experiences with cyclic injections of low-dose recombinant interleukin 2 in diverse autoimmune diseases have demonstrated increased numbers of circulating regulatory T cells, preserved regulatory function, improved clinical manifestations, and excellent tolerance. Similar improvements have been recognized in one of two patients with refractory autoimmune hepatitis. In conclusion, interferon 2 has biological actions that favor the immune suppressor functions of regulatory T cells, and low-dose regimens in preliminary studies encourage its rigorous investigation in autoimmune hepatitis.

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Section: Overviewmentioning

confidence: 99%

Exploring the Pathogenic Role and Therapeutic Implications of Interleukin 2 in Autoimmune Hepatitis

Czaja

2020

Dig Dis Sci

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“…The expression of cell death-related genes was not altered in GILZ KO mice, thus we concluded that the enhanced susceptibility to CCl 4 -induced LF depends on other cellular processes. LF development is strictly associated with inflammation 4 , 70 – 72 . We found that GILZ controls the leukocyte recruitment to the liver during initial and chronic phases of LF development, following CCl 4 -induced liver damage.…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoid-induced leucine zipper regulates liver fibrosis by suppressing CCL2-mediated leukocyte recruitment

et al. 2021

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Liver fibrosis (LF) is a dangerous clinical condition with no available treatment. Inflammation plays a critical role in LF progression. Glucocorticoid-induced leucine zipper (GILZ, encoded in mice by the Tsc22d3 gene) mimics many of the anti-inflammatory effects of glucocorticoids, but its role in LF has not been directly addressed. Here, we found that GILZ deficiency in mice was associated with elevated CCL2 production and pro-inflammatory leukocyte infiltration at the early LF stage, resulting in enhanced LF development. RNA interference-mediated in vivo silencing of the CCL2 receptor CCR2 abolished the increased leukocyte recruitment and the associated hepatic stellate cell activation in the livers of GILZ knockout mice. To highlight the clinical relevance of these findings, we found that TSC22D3 mRNA expression was significantly downregulated and was inversely correlated with that of CCL2 in the liver samples of patients with LF. Altogether, these data demonstrate a protective role of GILZ in LF and uncover the mechanism, which can be targeted therapeutically. Therefore, modulating GILZ expression and its downstream targets represents a novel avenue for pharmacological intervention for treating LF and possibly other liver inflammatory disorders.

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“…The liver receives blood from both the portal vein and the hepatic artery. In the portal vein, the liver confronts various antigens from digested food and the gut microbiome under physiological conditions (13). The immune reaction is tightly controlled and regulated, generating liver-protective immunity while these antigens pass through sinusoids.…”

Section: Introductionmentioning

confidence: 99%

Immune Tolerance Induction Using Cell-Based Strategies in Liver Transplantation: Clinical Perspectives

et al. 2020

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Liver transplantation (LT) has become the best chance and a routine practice for patients with end-stage liver disease and small hepatocellular carcinoma. However, lifelong immunosuppressive regimens could lead to many post-LT complications, including cancer recurrence, infections, dysmetabolic syndrome, and renal injury. Impeccable management of immunosuppressive regimens is indispensable to ensure the best long-term prognosis for LT recipients. This is challenging for these patients, who probably have a post-LT graft survival of more than 10 or even 20 years. Approximately 20% of patients after LT could develop spontaneous operational tolerance. They could maintain normal graft function and histology without any immunosuppressive regimens. Operational tolerance after transplantation has been an attractive and ultimate goal in transplant immunology. The liver, as an immunoregulatory organ, generates an immune hyporesponsive microenvironment under physiological conditions. In this regard, LT recipients may be ideal candidates for studies focusing on operative tolerance. Cell-based strategies are one of the most promising methods for immune tolerance induction, including chimerism induced by hematopoietic stem cells and adoptive transfer of regulatory T cells, regulatory dendritic cells, regulatory macrophages, regulatory B cells, and mesenchymal stromal cells. The safety and the efficacy of many cell products have been evaluated by prospective clinical trials. In this review, we will summarize the latest perspectives on the clinical application of cell-based strategies in LT and will address a number of concerns and future directions regarding these cell products.

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Immune Cell Trafficking to the Liver

Cited by 33 publications

References 259 publications

Exploring the Pathogenic Role and Therapeutic Implications of Interleukin 2 in Autoimmune Hepatitis

Exploring the Pathogenic Role and Therapeutic Implications of Interleukin 2 in Autoimmune Hepatitis

Glucocorticoid-induced leucine zipper regulates liver fibrosis by suppressing CCL2-mediated leukocyte recruitment

Immune Tolerance Induction Using Cell-Based Strategies in Liver Transplantation: Clinical Perspectives

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