Cross talk of the immune system in the adipose tissue and the liver in non-alcoholic steatohepatitis: Pathology and beyond

Abstract

Non-alcoholic steatohepatitis (NASH) is considered to be the hepatic manifestation of the metabolic syndrome, thus has a tight correlation with systemic metabolic impairment. The complex mechanisms underlying the pathogenesis of NASH involve different organs and systems that cross talk together contributing to the onset of NASH. A crucial role is played by inflammatory mediators, especially those deriving from the adipose tissue and the liver, which are involved in the cascade of inflammation, fibrosis and eventually tumorigenesis. In this setting cytokines and adipokines as well as immunity are emerging drivers of the key features of NASH. The immune system participates in this process with disturbances of the cells constituting both the innate and the adaptive immune systems that have been reported in different organs, such as in the liver and in the adipose tissue, in clinical and preclinical studies. The role of the immune system in NASH is increasingly studied, not only because of its contribution to the pathogenetic mechanisms of NASH but also because of the new potential therapeutic options it offers in this setting. Indeed, novel treatments acting on the immune system could offer new options in the management of NASH and the correlated clinical consequences.Key words: Non-alcoholic steatohepatitis; Immune system; Adipokines; Inflammation; Fibrosis Core tip: Non-alcoholic steatohepatitis (NASH) is considered to be the hepatic manifestation of the metabolic syndrome, thus has a tight correlation with systemic metabolic impairment. The complex mechanisms underlying the pathogenesis of NASH involve different organs, including liver, adipose tissue and immune system, which cross talk together contributing to the onset of NASH. Increasing interest has been aroused by the role of the immune system in NASH, not only because of its Cross talk of the immune system in the adipose tissue and the liver in non-alcoholic steatohepatitis: Pathology and beyond contribution to the pathogenetic mechanisms of NASH but also considering the new potential therapeutic options in this setting.Vonghia L, Francque S. Cross talk of the immune system in the adipose tissue and the liver in non-alcoholic steatohepatitis: Pathology and beyond.

Innate Immunity and Inflammation in NAFLD/NASH

“…Signaling from a dysfunctional adipose tissue is also involved in hepatic innate immunity activation in NAFLD/NASH [83]. Insulin resistant adipose tissue undergoes uncontrolled lipolysis increasing serum free fatty acids available for ectopic tissue deposition.…”

“…In the liver, as discussed earlier, fatty acids may directly contribute to KCs activation via direct TLR2/4 binding [84]. Also, dysfunctional adipose tissue also exhibits an imbalance in adipokine production consisting in a reduced production of adiponectin and increased production of leptin and resistin [83]. …”

Immune Imbalances in Non-Alcoholic Fatty Liver Disease: From General Biomarkers and Neutrophils to Interleukin-17 Axis Activation and New Therapeutic Targets

“…In the liver, the IL-17 exacerbates the liver tissue inflammation (29, 105, 106), enhancing tissue leukocytes infiltration (107), is a mediator of the cross talk between the immune system and liver cells (85, 108–111), has a profibrotic effect as noted in liver biopsies (70, 85, 86), among several others effects. In addition, is a potent stimulator of production of other inflammatory mediators, such as tumor necrosis factor (TNF-α), interleukin-1 (IL-1), and IL-6 (85, 111, 112).…”

Immunotherapy with oral administration of humanized anti-CD3 monoclonal antibody: a novel gut-immune system-based therapy for metaflammation and NASH

“…NASH can progress further to liver cirrhosis and eventually to hepatocellular carcinoma [6]. The immune system in NASH is being recognized increasingly to contribute to the pathogenic mechanisms of NASH and as a potential therapeutic target [7]. The low-grade inflammatory state present in obesity promotes the progression of NAFLD to NASH.…”

“…Activation of the innate immune system and increased release of proinflammatory cytokines and other mediators play a role in various stages of disease progression. Inflammatory mediators, including those that are derived from adipose tissue and the liver, are involved in the cascade of inflammation, fibrosis and eventually tumorigenesis [7]. A cytokine imbalance is associated with Th17 differentiation, fibrogenesis and steatohepatitis [19].…”