The liver works as a school to educate regulatory immune cells

Li, Fenglei; Tian, Zhigang

doi:10.1038/cmi.2013.7

Cited by 77 publications

(57 citation statements)

References 143 publications

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“…Although this effect prevents the development of sepsis or systemic inflammation, this effect also is the main contributor to immunosuppression and mortality [54]. Endotoxin tolerance has been observed in patients with sepsis, acute liver failure, and cirrhosis [55].…”

Section: Liver Immune Response In Sepsismentioning

confidence: 99%

The Role of the Liver in Sepsis

Yan

2014

International Reviews of Immunology

430

352

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Despite the progress made in the clinical management of sepsis, sepsis morbidity and mortality rates remain high. The inflammatory pathogenesis and organ injury leading to death from sepsis are not fully understood for vital organs, especially the liver. Only recently has the role of the liver in sepsis begun to be revealed. Pre-existing liver dysfunction is a risk factor for the progression of infection to sepsis. Liver dysfunction after sepsis is an independent risk factor for multiple organ dysfunction and sepsis-induced death. The liver works as a lymphoid organ in response to sepsis. Acting as a double-edged sword in sepsis, the liver-mediated immune response is responsible for clearing bacteria and toxins but also causes inflammation, immunosuppression, and organ damage. Attenuating liver injury and restoring liver function lowers morbidity and mortality rates in patients with sepsis. This review summarizes the central role of liver in the host immune response to sepsis and in clinical outcomes.

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Section: Liver Immune Response In Sepsismentioning

confidence: 99%

The Role of the Liver in Sepsis

Yan

2014

International Reviews of Immunology

430

352

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“…Daclizumab therapy was associated with a significant expansion of regulatory CD56 bright NK cells in vivo and a gradual decline in circulating CD4 + and CD8 + T cells, providing supporting evidence for the existence of an immunoregulatory pathway through which activated CD56 bright NK cells inhibit T‐cell survival . Defined by the differential expression of a combination of CD27 and CD11b, analysis of NK cell subsets indicated that the immature subset was dominant in the liver and that the immature CD27 + CD11b − hepatic NK cell subset was protective against liver metastasis, indicating that the liver maintains a special local immune tolerogenic microenvironment and educates NK tolerant cells …”

Section: Regulatory Nk Cells In Organsmentioning

confidence: 99%

Subsets of human natural killer cells and their regulatory effects

2014

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SummaryHuman natural killer (NK) cells have distinct functions as NK tolerant , NK cytotoxic and NK regulatory cells and can be divided into different subsets based on the relative expression of the surface markers CD27 and CD11b. CD27 + NK cells, which are abundant cytokine producers, are numerically in the minority in human peripheral blood but constitute the large population of NK cells in cord blood, spleen, tonsil and decidua tissues. Recent data suggest that these NK cells may have immunoregulatory properties under certain conditions. In this review, we will focus on these new NK cell subsets and discuss how regulatory NK cells may serve as rheostats or sentinels in controlling inflammation and maintaining immune homeostasis in various organs.

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“…12 More importantly, the percentage of NK cells in the liver is known to be nearly five times greater than the percentages in blood or spleen. 13,14 These liver-residing NK cells exert unique phenotypic and functional characteristics, such as immunological memory, suggesting the critical role of NK cells in the liver. 15,16 However, the percentage and absolute number of liver NK cells decrease significantly during the development and progression of HCC.…”

Section: Introductionmentioning

confidence: 99%

NK cell receptor imbalance and NK cell dysfunction in HBV infection and hepatocellular carcinoma

et al. 2014

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Hepatocellular carcinoma (HCC) is currently the third leading cause of cancer mortality and a common poor-prognosis malignancy due to postoperative recurrence and metastasis. There is a significant correlation between chronic hepatitis B virus (HBV) infection and hepatocarcinogenesis. As the first line of host defense against viral infections and tumors, natural killer (NK) cells express a large number of immune recognition receptors (NK receptors (NKRs)) to recognize ligands on hepatocytes, liver sinusoidal endothelial cells, stellate cells and Kupffer cells, which maintain the balance between immune response and immune tolerance of NK cells. Unfortunately, the percentage and absolute number of liver NK cells decrease significantly during the development and progression of HCC. The abnormal expression of NK cell receptors and dysfunction of liver NK cells contribute to the progression of chronic HBV infection and HCC and are significantly associated with poor prognosis for liver cancer. In this review, we focus on the role of NK cell receptors in anti-tumor immune responses in HCC, particularly HBV-related HCC. We discuss specifically how tumor cells evade attack from NK cells and how emerging understanding of NKRs may aid the development of novel treatments for HCC. Novel mono-and combination therapeutic strategies that target the NK cell receptor-ligand system may potentially lead to successful and effective immunotherapy in HCC. Keywords: activating receptor; hepatocellular carcinoma; inhibitory receptor; natural killer cell; natural killer receptor INTRODUCTION Hepatocellular carcinoma (HCC) is currently the third leading cause of cancer mortality and a common poor-prognosis malignancy due to postoperative recurrence and metastasis. 1 Common clinical risk factors for HCC include hepatitis B virus (HBV)/hepatitis C virus (HCV) infection, heavy alcohol intake, steatohepatitis and diabetes. 2 Approximately 50% of HCC cases worldwide can be attributed to chronic HBV infection (CHB) and almost 75% of HCC cases occur in developing countries where HBV is endemic. 3,4 According to statistics, older male patients who are infected with HBV genotype C or co-infected with HCV, have high levels of viral load and have been exposed to the aflatoxin, or older male patients who have a family history of HCC tend to have a high risk of developing HCC. [5][6][7] Accumulating clinical and epidemiological evidence shows a significant correlation between chronic HBV infection and hepatocarcinogenesis. However, the underlying mechanisms

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The liver works as a school to educate regulatory immune cells

Cited by 77 publications

References 143 publications

The Role of the Liver in Sepsis

The Role of the Liver in Sepsis

Subsets of human natural killer cells and their regulatory effects

NK cell receptor imbalance and NK cell dysfunction in HBV infection and hepatocellular carcinoma

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