Interleukin-30 Suppresses Not Only CD4+ T Cells but Also Regulatory T Cells in Murine Primary Biliary Cholangitis

被引:3
作者
Chen, Hung-Wen [1 ]
Lin, Chia-, I [1 ]
Chuang, Ya-Hui [1 ,2 ]
机构
[1] Natl Taiwan Univ, Coll Med, Dept Clin Lab Sci & Med Biotechnol, Taipei 10617, Taiwan
[2] Natl Taiwan Univ Hosp, Dept Lab Med, Taipei 10617, Taiwan
关键词
primary biliary cholangitis; autoimmune disease; interleukin-30; immune therapy; CD4(+) T cells; AUTOIMMUNE CHOLANGITIS; CIRRHOSIS; LIVER; IL-27P28; IL-30; GAMMA; MICE; TH1;
D O I
10.3390/biomedicines9081031
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Primary biliary cholangitis (PBC) is a chronic liver autoimmune disease with augmented T helper (Th) 1 and corresponding cytokine IFN-gamma immune responses. Using 2-octynoic acid (2-OA) coupled to OVA (2-OA-OVA)-induced mouse models of autoimmune cholangitis (inducible chemical xenobiotic models of PBC), our previous study demonstrated that overexpression of IFN-gamma in the model mice enhanced liver inflammation upon disease initiation, but subsequently led to the suppression of chronic inflammation with an increase in interleukin-30 (IL-30) levels. In this study, we investigated whether IL-30 had an immunosuppressive function and whether it could be part of an immune therapeutic regimen for PBC, by treating model mice with murine IL-30-expressing recombinant adeno-associated virus (AAV-mIL-30). We first defined the effects of AAV-mIL-30 in vivo by administering it to a well-known concanavalin A (ConA)-induced hepatitis model of mice and found that AAV-mIL-30 reduced the numbers of activated CD25(+)CD4(+) T cells and the levels of serum IFN-gamma and IL-12. In autoimmune cholangitis, decreased numbers of activated CD4(+) T cells and Foxp3(+) regulatory T cells were noted in the mice treated with AAV-mIL-30 at 3 weeks after the 2-OA-OVA immunization. Treatment with IL-30 did not change the features of autoimmune cholangitis including autoantibodies, cell infiltration, and collagen deposition in the liver at 11 weeks of examination. However, increased levels of cytokines and chemokines were observed. These results suggest that IL-30 suppresses not only CD4(+) T cells but also regulatory T cells. Additionally, the administration of IL-30 did not suppress liver inflammation in the murine model of PBC.
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页数:12
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