Isolation and characterization of LIGHT (TNFSF14) gene homologue in zebrafish (Danio rerio)

Tian, Ai-ying; Yang, Huijuan; Zhu, Shicheng; Zhang, Yushun; Jiang, Zheng-an; Song, Jiuzhou; Liu, Hongzhen; Zhang, Shuangquan

doi:10.1016/j.intimp.2012.09.015

Cited by 8 publications

(2 citation statements)

References 28 publications

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“…7B). The expression pattern was consistent with those of other teleost LIGHT (25,80,81) and mammalian LIGHT (45,73,82). Additionally, the expression pattern of fugu LIGHT was similar to that of fugu LTbR except in PBLKs.…”

Section: Cytoplasmic Traf Binding Domains Of Fish Ltbrsupporting

confidence: 81%

Original Ligand for LTβR Is LIGHT: Insight into Evolution of the LT/LTβR System

Maeda

Suetake

Odaka

et al. 2018

The Journal of Immunology

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The lymphotoxin (LT)/LTβ receptor (LTβR) axis is crucial for the regulation of immune responses and development of lymphoid tissues in mammals. Despite the importance of this pathway, the existence and function of LT and LTβR remain obscure for nonmammalian species. In this study, we report a nonmammalian LTβR and its ligand. We demonstrate that TNF-New (TNFN), which has been considered orthologous to mammalian LT, was expressed on the cell surface as a homomer in vitro. This different protein structure indicates that TNFN is not orthologous to mammalian LTα and LTβ. Additionally, we found that LTβR was conserved in teleosts, but the soluble form of recombinant fugu LTβR did not bind to membrane TNFN under the circumstance tested. Conversely, the LTβR recombinant bound to another ligand, LIGHT, similar to that of mammals. These findings indicate that teleost LTβR is originally a LIGHT receptor. In the cytoplasmic region of fugu LTβR, recombinant fugu LTβR bound to the adaptor protein TNFR-associated factor (TRAF) 2, but little to TRAF3. This difference suggests that teleost LTβR could potentially activate the classical NF-κB pathway with a novel binding domain, but would have little ability to activate an alternative one. Collectively, our results suggested that LIGHT was the original ligand for LTβR, and that the teleost immune system lacked the LT/LTβR pathway. Acquisition of the LT ligand and TRAF binding domain after lobe-finned fish may have facilitated the sophistication of the immune system and lymphoid tissues.

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Section: Cytoplasmic Traf Binding Domains Of Fish Ltbrsupporting

confidence: 81%

Original Ligand for LTβR Is LIGHT: Insight into Evolution of the LT/LTβR System

Maeda

Suetake

Odaka

et al. 2018

The Journal of Immunology

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“…The BTLA, HVEM, and LIGHT immune checkpoint regulators have become increasingly explored because of their important modulatory roles in immunity and extensive involvement in various diseases of humans and other mammals (28,32). However, the occurrence and functions of these checkpoint molecules in nonmammalian species remain poorly understood (45). In the current study, we identified Btla, Hvem, and Light homologs from zebrafish.…”

Section: Discussionmentioning

confidence: 90%

BTLA–HVEM Checkpoint Axis Regulates Hepatic Homeostasis and Inflammation in a ConA-Induced Hepatitis Model in Zebrafish

Shi

Shao

et al. 2019

The Journal of Immunology

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The BTLA2HVEM checkpoint axis plays extensive roles in immunomodulation and diseases, including cancer and autoimmune disorders. However, the functions of this checkpoint axis in hepatitis remain limited. In this study, we explored the regulatory role of the Btla-Hvem axis in a ConA-induced hepatitis model in zebrafish. Results showed that Btla and Hvem were differentially expressed on intrahepatic Cd8 + T cells and hepatocytes. Knockdown of Btla or Hvem significantly promoted hepatic inflammation. Btla was highly expressed in Cd8 + T cells in healthy liver but was downregulated in inflamed liver, as evidenced by a disparate proportion of Cd8 + Btla + and Cd8 + Btla-T cells in individuals without or with ConA stimulation. Cd8 + Btla + T cells showed minimal cytotoxicity to hepatocytes, whereas Cd8 + Btla-T cells were strongly reactive. The depletion of Cd8 + Btla-T cells reduced hepatitis, whereas their transfer enhanced hepatic inflammation. These observations indicate that Btla endowed Cd8 + Btla + T cells with self-tolerance, thereby preventing them from attacking hepatocytes. Btla downregulation deprived this tolerization. Mechanistically, Btla-Hvem interaction contributed to Cd8 + Btla + T cell tolerization, which was impaired by Hvem knockdown but rescued by soluble Hvem protein administration. Notably, Light was markedly upregulated on Cd8 + Btla-T cells, accompanied by the transition of Cd8 + Btla + Lightto Cd8 + Btla-Light + T cells during hepatitis, which could be modulated by Cd4 + T cells. Light blockade attenuated hepatitis, thereby suggesting the positive role of Light in hepatic inflammation. These findings provide insights into a previously unrecognized Btla-Hvem-Light regulatory network in hepatic homeostasis and inflammation, thus adding a new potential therapeutic intervention for hepatitis.

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Fish TNF and TNF receptors

Xiao

Zou

2020

Sci. China Life Sci.

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Isolation and characterization of LIGHT (TNFSF14) gene homologue in zebrafish (Danio rerio)

Cited by 8 publications

References 28 publications

Original Ligand for LTβR Is LIGHT: Insight into Evolution of the LT/LTβR System

Original Ligand for LTβR Is LIGHT: Insight into Evolution of the LT/LTβR System

BTLA–HVEM Checkpoint Axis Regulates Hepatic Homeostasis and Inflammation in a ConA-Induced Hepatitis Model in Zebrafish

Fish TNF and TNF receptors

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