| Autor: |
Chengying Yang, Yongwen Chen, Guoning Guo, Hong Li, Dayan Cao, Huan Xu, Sheng Guo, Lei Fei, Weiming Yan, Qing Ning, Lixin Zheng, Yuzhang Wu |
| Předmět: |
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| Zdroj: |
Gut; Aug2013, Vol. 62 Issue 8, p1204-1213, 10p, 4 Color Photographs, 3 Graphs |
| Abstrakt: |
Objectives: Fulminant viral hepatitis (FH) remains a serious clinical problem for which the underlying pathogenesis remains unclear. The B and T lymphocyte attenuator (BTLA) is an immunoglobulin-domaincontaining protein that has the capacity to maintain peripheral tolerance and limit immunopathological damage during immune responses. However, its precise role in FH has yet to be investigated. Design: BTLA-deficient (BTLA-/-) mice and their wildtype littermates were infected with murine hepatitis virus strain-3 (MHV-3), and the levels of tissue damage, cell apoptosis, serum liver enzymes, fibrinogen-like protein 2 (FGL2) and cytokine production were measured and compared. Survival rate was studied after MHV-3 infection with or without adoptive transferring macrophages. Results: FGL2 production, liver and spleen damage, and mortality were significantly reduced in BTLA-/- mice infected with MHV-3. This effect is due to rapid, TRAIL (TNF-related apoptosis-inducing ligand)-dependent apoptosis of MHV-3-infected macrophages in BTLA-/- mice. The early loss of macrophages resulted in reduced pathogenic tumour necrosis factor α (TNFα) and FGL2 levels and lower viral titres. The importance of TNFα in MHV-3-induced pathology was demonstrated by increased mortality in TNFα-treated MHV-3-infected BTLA-/- mice, whereas TNFα-/- mice were resistant to the infection. Moreover, adoptively transferring macrophages to BTLA-/- mice caused sensitisation, whereas blocking BTLA protected wild-type mice from virus-induced FH mortality. Conclusions: BTLA promotes the pathogenesis of virusinduced FH by enhancing macrophage viability and function. Targeting BTLA may be a novel strategy for the treatment of FH. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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