IL-17C/IL-17RE Augments T Cell Function in Autoimmune Hepatitis

Area of Science:

• Immunology
• Hepatology
• Molecular Biology

Background:

• Autoimmune hepatitis (AIH) is a global health concern with unknown etiology, leading to ineffective treatments.
• Current understanding of AIH pathogenesis remains incomplete, hindering therapeutic advancements.

Purpose of the Study:

• To investigate the role of the Interleukin-17C (IL-17C) and its receptor Interleukin-17 Receptor E (IL-17RE) axis in Concanavalin A (Con A)-induced hepatitis.
• To elucidate the molecular mechanisms by which IL-17C contributes to liver injury in autoimmune hepatitis.

Main Methods:

• Analysis of IL-17C expression in human and mouse liver samples with autoimmune hepatitis.
• Assessment of the necessity of IL-17C and IL-17RE in Con A-induced liver damage models.
• Investigation of the impact of IL-17C on intrahepatic CD4+ T cell and Natural Killer (NK) cell activation.

Main Results:

• Elevated IL-17C expression was observed in liver tissues of both human and mouse autoimmune hepatitis.
• Both IL-17C produced by hepatocytes and IL-17RE on liver-resident T cells were essential for Con A-induced liver injury.
• IL-17C enhanced IL-2 expression in intrahepatic CD4+ T cells, subsequently promoting NK cell activation and liver damage.

Conclusions:

• The IL-17C/IL-17RE axis plays a critical and indispensable role in the pathogenesis of autoimmune hepatitis.
• This axis represents a potential novel therapeutic target for managing autoimmune hepatitis and related liver diseases.