| First Author | Fang X | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 2 | Pages | e31174 |
| PubMed ID | 22347449 | Mgi Jnum | J:185232 |
| Mgi Id | MGI:5427790 | Doi | 10.1371/journal.pone.0031174 |
| Citation | Fang X, et al. (2012) Ameliorated ConA-induced hepatitis in the absence of PKC-theta. PLoS One 7(2):e31174 |
| abstractText | Severe liver injury that occurs when immune cells mistakenly attack an individual's own liver cells leads to autoimmune hepatitis. In mice, acute hepatitis can be induced by concanavalin A (ConA) treatment, which causes rapid activation of CD1d-positive natural killer (NK) T cells. These activated NKT cells produce large amounts of cytokines, which induce strong inflammation that damages liver tissues. Here we show that PKC-theta(-/-) mice were resistant to ConA-induced hepatitis due to essential function of PKC-theta in NKT cell development and activation. A dosage of ConA (25 mg/kg) that was lethal to wild-type (WT) mice failed to induce death resulting from liver injury in PKC-theta(-/-) mice. Correspondingly, ConA-induced production of cytokines such as IFNgamma, IL-6, and TNFalpha, which mediate the inflammation responsible for liver injury, were significantly lower in PKC-theta(-/-) mice. Peripheral NKT cells had developmental defects at early stages in the thymus in PKC-theta(-/-) mice, and as a result their frequency and number were greatly reduced. Furthermore, PKC-theta(-/-) bone marrow adoptively transferred to WT mice displayed similar defects in NKT cell development, suggesting an intrinsic requirement for PKC-theta in NKT cell development. In addition, upon stimulation with NKT cell-specific lipid ligand, peripheral PKC-theta(-/-) NKT cells produced lower levels of inflammatory cytokines than that of WT NKT cells, suggesting that activation of NKT cells also requires PKC-theta. Our results suggest PKC-theta is an essential molecule required for activation of NKT cell to induce hepatitis, and thus, is a potential drug target for prevention of autoimmune hepatitis. |
