Expression of B and T lymphocyte attenuator (BTLA) in macrophages contributes to the fulminant hepatitis caused by murine hepatitis virus strain-3

Yang, Chengying; Chen, Yongwen; Guo, Guoning; Li, Hong; Cao, Dayan; Xu, Huan; Guo, Sheng; Lei, Fei; Yan, Weiming; Ning, Qing; Zheng, Lixin; Wu, Yuzhang

doi:10.1136/gutjnl-2012-302239

Cited by 34 publications

(50 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hobit mediates the development and retention of Trm cells and NKT cells in non-lymphoid organs and other nonbarrier tissues and may provide immediate immunological protection against re-infections. BTLA is an immunoglobulin-like molecule belonging to the B7 family, which relays inhibitory signals that suppress the immune response (23). Moreover, the interaction between BTLA and its ligand has been reported to be actively involved in the adaptive immune response (24).…”

Section: Discussionmentioning

confidence: 99%

Association of biobehavioral factors with non-coding RNAs in cervical cancer

Liu

Dai

et al. 2018

BST

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Association of biobehavioral factors with non-coding RNAs in cervical cancer

Liu

Dai

et al. 2018

BST

View full text Add to dashboard Cite

“…[8,12,17,19,21,25] . A stretch of hydrophobic amino acids at N-terminus of FGL2 may serve as signal peptide for sFGL2 secretion [14] , but the mechanism whereby sFGL2 is cleaved and released outside of the host cell remains to be determined.…”

Section: Structure and Functionmentioning

confidence: 99%

“…Ning et al [57,58] demonstrated that the nucleocapsid protein of MHV3 was capable of activating transcription of mouse Fgl2 gene in vitro . Serum level of sFGL2 was shown to correlate with liver cytopathology among the mice infected by MHV3 [19] . More compelling evidence suggesting that FGL2 might contribute to pathogenesis of viral infection comes from the elegant studies by Shalev et al [27] and by Marsden et al [23] , who have demonstrated that MHV3 caused fibrin deposition and hepatocellular necrosis only in Fgl2 +/+ mice but not in Fgl2 −/− mice.…”

Section: Pathogenesismentioning

confidence: 99%

“…First, MHV3 induced significantly greater apoptosis of macrophages from A/J mice than from BALB/cJ mice [64] . MHV3 is propagated in macrophages [19] . Apoptosis of macrophages might decrease the extent of viral replication and result in higher MHV3 viral load in BALB/cJ than in A/J mice.…”

Section: Pathogenesismentioning

confidence: 99%

“…Apoptosis of macrophages might decrease the extent of viral replication and result in higher MHV3 viral load in BALB/cJ than in A/J mice. Additionally, macrophages are a source of FGL2 production [19,56,64] . Fgl2 +/+ - macrophages exhibited a robust procoagulant response to MHV3; whereas procoagulant activity from Fgl2 −/− macrophages exposed to MHV3 was comparable to the control levels [23] .…”

Section: Pathogenesismentioning

confidence: 99%

See 2 more Smart Citations

Physiological functions and clinical implications of fibrinogen-like 2: A review

Yang

Hooper

2013

WJCID

View full text Add to dashboard Cite

Fibrinogen-like 2 (FGL2) encompasses a transmembrane (mFGL2) and a soluble (sFGL2) form with differential tertiary structure and biological activities. Typically, mFGL2 functions as prothrombinase that is capable of initiating coagulation in tissue without activation of the blood clotting cascade, whereas sFGL2 largely acts as an immunosuppressor that can repress proliferation of alloreactive T lymphocytes and maturation of bone marrow dendritic cells. Protein sequences of FGL2 exhibit evolutionary conservation across wide variety of species, especially at the carboxyl terminus that contains fibrinogen related domain (FRED). The FRED of FGL2 confers specificity and complexity in the action of FGL2, including receptor recognition, calcium affiliation, and substrate binding. Constitutive expression of FGL2 during embryogenesis and in mature tissues suggests FGL2 might be physiologically important. However, excessive induction of FGL2 under certain medical conditions (e.g., pathogen invasion) could trigger complement activation, inflammatory response, cellular apoptosis, and immune dysfunctions. On the other hand, complete absence of FGL2 is also detrimental as lack of FGL2 can cause autoimmune glomerulonephritis and acute cellular rejection of xenografts. All these roles involve mFGL2, sFGL2, or their combination. Although it is not clear how mFGL2 is cleaved off its host cells and secreted into the blood, circulating sFGL2 has been found correlated with disease severity and viral loading among patients with human hepatitis B virus or hepatitis C virus infection. Further studies are warranted to understand how FGL2 expression is regulated under physiological and pathological conditions. Even more interesting is to determine whether mFGL2 can fulfill an immunoregulatory role through its FRED at carboxyl end of the molecule and, and vice versa, whether sFGL2 is procoagulant upon binding to a target cell. Knowledge in this area should shed light on development of sFGL2 as an alternative immunosuppressive agent for organ transplantation or as a biomarker for predicting disease progression, monitoring therapeutic effects, and targeting FGL2 for repression in ameliorating fulminant viral hepatitis.

show abstract

C5a/C5aR pathway is essential for the pathogenesis of murine viral fulminant hepatitis by way of potentiating Fgl2/fibroleukin expression

Chen

Yang

et al. 2014

Hepatology

View full text Add to dashboard Cite

Viral fulminant hepatitis (FH) remains a serious clinical problem with very high mortality. Lacking understanding of FH pathogenesis has in essence hindered efficient clinical treatment. Inferring from a correlation observed between the genetic differences in the complement component 5 (C5) and the susceptibility of mouse strains to murine hepatitis virus strain-3 (MHV-3) infections, we propose that excessive complement activation plays a critical role in the development of FH. We show that MHV-3 infection causes massive complement activation, along with a rapid increase in serum C5a levels and quick development of FH in susceptible strains. Mice deficient in the C5a receptor (C5aR) or the susceptible strains treated with C5aR antagonists (C5aRa) exhibit significant attenuation of the disease, accompanied by a remarkable reduction of hepatic fibrinogen-like protein 2 (Fgl2), a hallmark protein that causes necrosis of infected livers. In accordance, biopsy of FH patients shows a dramatic increase of Fgl2 expression, which correlates with C5aR up-regulation in the liver. In vitro C5a administration accelerates MHV-3-induced Fgl2 secretion by macrophages. Furthermore, inhibiting ERK1/2 and p38 efficiently blocks C5a-mediated Fgl2 production during viral infections. Conclusion: These data provide evidence that mouse susceptibility to MHV-3-induced FH may rely on C5a/C5aR interactions, for which ERK1/2 and p38 pathways participate in up-regulating Fgl2 expression. Inhibition of C5a/C5aR interactions is expected to be beneficial in the clinical treatment of FH patients. (HEPATOLOGY 2014;60:114-124)

show abstract

Expression of B and T lymphocyte attenuator (BTLA) in macrophages contributes to the fulminant hepatitis caused by murine hepatitis virus strain-3

Abstract: BTLA promotes the pathogenesis of virus-induced FH by enhancing macrophage viability and function. Targeting BTLA may be a novel strategy for the treatment of FH.

Cited by 34 publications

References 29 publications

Association of biobehavioral factors with non-coding RNAs in cervical cancer

Association of biobehavioral factors with non-coding RNAs in cervical cancer

Physiological functions and clinical implications of fibrinogen-like 2: A review

C5a/C5aR pathway is essential for the pathogenesis of murine viral fulminant hepatitis by way of potentiating Fgl2/fibroleukin expression

Contact Info

Product

Resources

About