The Role of IL-35 in the Pathophysiological Processes of Liver Disease

Abstract

It is known that liver diseases have several characteristics of massive lipid accumulation and lipid metabolic disorder, and are divided into liver inflammation, liver fibrosis, liver cirrhosis (LC), and hepatocellular carcinoma (HCC) in patients. Interleukin (IL)-35, a new-discovered cytokine, can protect the liver from the environmental attack by increasing the ratio of Tregs (T regulatory cells) which can increase the anti-inflammatory cytokines and inhibit the proliferation of immune cellular. Interestingly, two opposite mechanisms (pro-inflammatory and anti-inflammatory) have connection with the ultimate formation of liver diseases, which suggest that IL-35 may play crucial function in the process of liver diseases through immunosuppressive regulation. Besides, some obvious advantages also imply that IL-35 can be considered as a new therapeutic target to control the progression of liver diseases, while its mechanism of function still needs further research.

Interleukin-35 and Thymoquinone nanoparticle-based intervention for liver protection against paracetamol-induced liver injury in rats

“…Liver disease is one of the most serious aliments in the world, with high incidence and mortality rate, and its prevalence is growing yearly ( Zhang et al, 2021 ). Chronic inflammation and oxidative stress are the main causes of liver disease, which can result in the assembly of an extracellular matrix that could lead to hepatitis, fibrosis, cirrhosis, and hepatocellular cancer ( Hu et al, 2021 ). Currently, there are limited effective options for treating liver illnesses.…”

“…IL-35 boosts the immunity and defends against damage and inflammation of liver commenced due to oxidative stress ( Egwuagu et al, 2015 ). It could exert its effect for protecting the liver by increasing the T-regulatory cells ratio, causing a surge in the anti-inflammatory cytokines and inhibition of immune cell proliferation ( Hu et al, 2021 ). Additionally, IL-35 is primarily released by immune cells, including the recently discovered B regulatory cells (CD4 + CD25 + ).…”

“…Earlier revisions illustrated that IL-35 has various roles in disease pathogenesis such as rheumatoid arthritis ( Ning et al, 2015 ), autoimmune encephalomyelitis, uveitis ( Wang et al, 2014 ), Hashimoto’s thyroiditis ( Yilmaz et al, 2016 ), multiple low dose streptozotocin ( Singh et al, 2015 ), allergic rhinitis ( Suzuki et al, 2017 ), liver disease ( Yang et al, 2020a ), cardiovascular diseases ( Posadas-Sánchez et al, 2017 ), and asthma ( Kanai et al, 2017 ). Anti-inflammatory and pro-inflammatory processes are involved in the developing liver disorders, suggesting that IL-35 may produce a noteworthy effect in the advance of liver diseases via immunosuppressive regulations ( Hu et al, 2021 , Hoshino et al, 2020 ).…”

“…Some of these findings also point to IL-35 as a viable pharmaceutical target for reducing the advancement of liver ailments; however further study is still needed to understand how it works. Overall, researches display that IL-35 has a tremendous impact on immune modulation during the progress of chronic hepatitis, liver fibrosis, liver cirrhosis (LC), and hepatocellular carcinoma (HCC) development ( Hu et al, 2021 ). Moreover, a previous in-depth study suggests that IL-35 can be utilized as a potential management approach to slow down the advancement of liver disorders, but more research is still needed to uncover its mechanism of action ( Hu et al, 2021 ).…”

B cells in autoimmune hepatitis: bystanders or central players?

“…IL-35 belongs to the IL-12 family and is a heterodimeric cytokine formed by p35 and EBI3 with immunosuppressive functions via increasing numbers of Tregs and regulatory B cells [ 127 ]. IL-35 fosters the generation of Tregs and inhibits CD4 + effector T cells like T H 1 and T H 17 cells [ 127 , 128 ]. In AIH, the hepatic expression of the IL-35 subunits p35 and EBI3 is elevated and correlates with liver inflammation and fibrosis, the level of p35 also with age and serum levels of IgG and transaminases [ 129 ].…”