Immune Netw.  2014 Apr;14(2):67-72. 10.4110/in.2014.14.2.67.

HVEM is a TNF Receptor with Multiple Regulatory Roles in the Mucosal Immune System

• Shui JW
• Kronenberg M

• KMID: 2168016
• DOI: http://doi.org/10.4110/in.2014.14.2.67

Abstract

The herpes virus entry mediator (HVEM) is a member of the tumor necrosis factor receptor superfamily (TNFRSF), and therefore it is also known as TNFRSF14 or CD270 (1,2). In recent years, we have focused on understanding HVEM function in the mucosa of the intestine, particularly on the role of HVEM in colitis pathogenesis, host defense and regulation of the microbiota (2,3,4). HVEM is an unusual TNF receptor because of its high expression levels in the gut epithelium, its capacity to bind ligands that are not members of the TNF super family, including immunoglobulin (Ig) superfamily members BTLA and CD160, and its bi-directional functionality, acting as a signaling receptor or as a ligand for the receptor BTLA. Clinically, Hvem recently was reported as an inflammatory bowel disease (IBD) risk gene as a result of genome wide association studies (5,6). This suggests HVEM could have a regulatory role influencing the regulation of epithelial barrier, host defense and the microbiota. Consistent with this, using mouse models, we have revealed how HVEM is involved in colitis pathogenesis, mucosal host defense and epithelial immunity (3,7). Although further studies are needed, our results provide the fundamental basis for understanding why Hvem is an IBD risk gene, and they confirm that HVEM is a mucosal gatekeeper with multiple regulatory functions in the mucosa.

Keyword

Mucosal immune response; Host defense; TNF; TNF receptor; Inflammation; Epithelial immunity; Innate immunity

MeSH Terms

Animals
Colitis
Epithelium
Genome-Wide Association Study
Humans
Immune System*
Immunity, Innate
Immunity, Mucosal
Immunoglobulins
Inflammation
Inflammatory Bowel Diseases
Intestines
Ligands
Mice
Microbiota
Mucous Membrane
Receptors, Tumor Necrosis Factor*
Virus Internalization
Immunoglobulins
Ligands
Receptors, Tumor Necrosis Factor

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