Other
13 Authors
- Li W,
- Dziedzic SA,
- Knipe DM,
- Najafov A,
- Broekema N,
- Zhu H,
- Qian L,
- Hu D,
- Ofengeim D,
- Jia N,
- Su Z,
- Yuan J,
- Barrett VJ
| First Author | Su Z | Year | 2019 |
| Journal | Cell Death Differ | Volume | 26 |
| Issue | 6 | Pages | 1077-1088 |
| PubMed ID | 30341420 | Mgi Jnum | J:296506 |
| Mgi Id | MGI:6467880 | Doi | 10.1038/s41418-018-0215-3 |
| Citation | Su Z, et al. (2019) ABIN-1 heterozygosity sensitizes to innate immune response in both RIPK1-dependent and RIPK1-independent manner. Cell Death Differ 26(6):1077-1088 |
| abstractText | ABIN-1 (encoded by the gene Tnip1) is a ubiquitin-binding protein that can interact with ubiquitin-editing enzyme A20 (encoded by the gene TNFAIP3) to restrain the activation of necroptosis and NF-kappaB activation. Genetic variants in the genes Tnip1 and TNFAIP3 are both strongly associated with susceptibility to autoimmune chronic inflammatory diseases such as psoriasis vulgaris and systemic lupus erythematosus (SLE) in humans. Here we investigated the mechanism by which ABIN-1 regulated innate immune responses. We show that ABIN-1 heterozygosity sensitizes cells to antiviral response by mediating NF-kappaB-dependent and RIPK1-independent expression of pattern recognition molecules, including TLR3, RIG-I, and MDA5, in MEFs. Furthermore, we demonstrate that increased interaction of ABIN-1 and A20 with prolonged poly(I:C) stimulation of WT cells leads to A20-dependent reduction of ABIN-1 protein. Finally, we show that ABIN-1 heterozygosity sensitizes innate immune response of Abin-1(+/)(-) mice in vivo by promoting the production of proinflammatory cytokines, which can be blocked upon inhibition of RIPK1 kinase. Inhibition of RIPK1 kinase activity in vivo partially reduces the expression of MDA5, RIG-I, and caspase-11 in Abin-1(+/)(-) mice but not in WT mice. Thus, we conclude that ABIN-1 is a suppressor of innate immune response and the interaction of ABIN-1 with A20 controls innate immunity response through the NF-kappaB pathway and in both RIPK1 kinase activity-independent and dependent manner. |
