Cellular interactions in self-directed immune-mediated liver diseases.

The lymphocyte population must traverse a complex path throughout their journey to the liver. The signals which these cells must detect, including cytokines, chemokines and other soluble factors, steer their course towards further crosstalk with other hepatic immune cells, hepatocytes and biliary epithelial cells. A series of specific chemokine receptors and adhesion molecules drive not only the recruitment, migration, and retention of these cells within the liver, but also their localisation.

Expression of E-cadherin by CD8 T cells promotes their invasion into biliary epithelial cells.

The presence of CD8 T cells in the cytoplasm of biliary epithelial cells (BEC) has been correlated with biliary damage associated with primary biliary cholangitis (PBC). Here, we characterise the mechanism of CD8 T cell invasion into BEC. CD8 T cells observed within BEC were large, eccentric, and expressed E-cadherin, CD103 and CD69.

Use of immunosuppression in non-transplant hepatology.

Human liver possesses a persistent and tightly regulated immune response. Maintaining this homeostatic state is the key to prevent pathological processes, as a failure in clearing dangerous stimuli, is associated with tissue damage. A dysregulation of the liver immune homeostasis is involved in many disease processes and the use of the immunosuppression aims to control the inflammatory response, where the physiologic mechanisms failed.

Gut-Liver Immune Traffic: Deciphering Immune-Pathogenesis to Underpin Translational Therapy.

The tight relationship between the gut and liver on embryological, anatomical and physiological levels inspired the concept of a gut-liver axis as a central element in the pathogenesis of gut-liver axis diseases. This axis refers to the reciprocal regulation between these two organs causing an integrated system of immune homeostasis or tolerance breakdown guided by the microbiota, the diet, genetic background, and environmental factors. Continuous exposure of gut microbiome, various hormones, drugs and toxins, or metabolites from the diet through the portal vein adapt the liver to maintain its tolerogenic state.

Type 2 Autoimmune Hepatitis and Nonadherence to Medication Correlate With Premature Birth and Risk of Postpartum Flare.

Autoimmune hepatitis (AIH) is an immune-mediated chronic liver disease that affects all ages, including women of childbearing age. Optimal management during pregnancy is poorly defined. We aimed to explore the clinical and biochemical course of AIH in the antenatal and postpartum periods, and assess factors associated with premature birth and postpartum flares.

Natural Killer Cells and Regulatory T Cells Cross Talk in Hepatocellular Carcinoma: Exploring Therapeutic Options for the Next Decade.

Despite major advances in immunotherapy, hepatocellular carcinoma (HCC) remains a challenging target. Natural Killer (NK) cells are crucial components of the anti-HCC immune response, which can be manipulated for immunotherapeutic benefit as primary targets, modulators of the tumour microenvironment and in synchronising with tumour antigen specific effector CD8 cells for tumour clearance. Regulatory T cells shape the anti-tumour response from effector T cells multiple suppressive mechanisms.

Breakdown in hepatic tolerance and its relation to autoimmune liver diseases.

The liver is a complex immunological organ. It has both immunogenic and tolerogenic capacity. Tolerogenic potential of human liver with its protective firewalls is required to guard the body against the continuous influx of microbial product from the gut via the sinusoids and biliary tree.

Autoimmune Hepatitis: Tolerogenic Immunological State During Pregnancy and Immune Escape in Post-partum.

The maternal immune system engages in a fine balancing act during pregnancy by simultaneously maintaining immune tolerance to the fetus and immune responses to protect against invading organisms. Pregnancy is an intricately orchestrated process where effector immune cells with fetal specificity are selectively silenced. This requires a sustained immune suppressive state not only by expansion of maternal Foxp3+ regulatory T cells (Tregs) but also by leaning the immune clock toward a Th2 dominant arm.

The hepatic microenvironment and regulatory T cells.

The human liver is regarded as a lymphoid organ that contributes to both local and systemic immune response. Intrahepatic immune cells including regulatory T cells (Tregs) reside in the hepatic microenvironment which is enriched with proinflammatory cytokines, chemokines and metabolites. In addition, the hepatic microenvironment has the unique ability to establish and maintain immune tolerance despite the continuous influx of the gut derived microbial products via the portal vein.