DcR3/TR6 modulates immune cell interactions.
DcR3/TR6, a secreted protein, is a member of TNF receptor family. Its ligands include FasL, LIGHT, and TL1A, all TNF family members. TR6 can interfere with FasL- or LTbetaR-mediated apoptosis; it can also inhibit T-cell costimulation by blocking the two-way signaling between TR2 and LIGHT, and the one-way signaling from TL1A to DR3. In this study, we discovered that TR6 was secreted by peripheral blood mononuclear cells (PBMC) stimulated by T-cell mitogens. It inhibited actin polymerization of T cells upon mitogen stimulation, and repress T-cell pseudopodium formation, which is known to be important for cell-cell interaction. As a consequence, T-cell aggregation stimulated by alloantigens, anti-CD3 or PHA was suppressed by either soluble or solid phase TR6-Fc. This result suggests that TR6 might regulate T-cell interaction with other cells such as antigen-presenting cells (APC) or their fellow T cells by preventing them from forming inseparable cell clusters, which are undesirable for the progression of immune responses.
Wan
Xiaochun
X
Laboratory of Transplantation Immunology, Notre Dame Hospital, University of Montreal, Montreal, Canada.
Shi
Guixiu
G
Semenuk
Mark
M
Zhang
Jun
J
Wu
Jiangping
J
D001483:Base Sequence; D001862:Bone Resorption; D002448:Cell Adhesion / Q000502:physiology; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology*; D008934:Mitogens / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor; D053323:Receptors, Tumor Necrosis Factor, Member 6b; D011994:Recombinant Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology
D017931:DNA Primers; D008562:Membrane Glycoproteins; D008934:Mitogens; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D053323:Receptors, Tumor Necrosis Factor, Member 6b; D011994:Recombinant Proteins