Conclusion
The protective effect of C6orf120 knockout against Con A-induced hepatitis may be due to the inhibition of NKT cell activation, restriction of cytokine and chemokine activities, inhibition of JAK-STAT and Fas/FasL signaling pathway activation, and reduction in liver inflammation and hepatocyte apoptosis.
Methods
An autoimmune hepatitis model was established with 35 mg/kg intravenous injection of concanavalin A (Con A) in C6orf120-knockout (C6orf120-/-) and wild-type (WT) rats. Rats were sacrificed after administering Con A for 0, 12, and 24 h. The peripheral blood, liver, spleen, and mesenteric lymph nodes were collected for follow-up studies.
Objective
To elucidate the role of the functional unknown gene C6orf120 in the pathogenesis of AIH and its mechanism of action, using C6orf120 knockout rats.
Results
C6orf120 knockout significantly decreased the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and improved the histological damage in Con A-induced autoimmune liver injury.Loss of C6orf120 function significantly increased the frequency of CD3+ CD161+ NKT cells in the peripheral blood, liver, and spleen; downregulated the expression of CD314 (NKG2D) in the liver, spleen, and mesenteric lymph nodes; reduced the expression of inflammatory cytokines and chemokines; and suppressed the mRNA and protein expression of Fas and FasL in the liver. Additionally, C6orf120 knockout significantly downregulated the expression of p-JAK1, p-JAK2, p-STAT1, and p-STAT3 in liver tissue.