Abstract
CD4+CD25+Foxp3+ regulatory T cells (Treg) are critical to the maintenance of immune tolerance. Treg are known to utilize a number of molecular pathways to control immune responses and maintain immune homeostasis. Fibrinogen-like protein 2 (FGL2) has been identified by a number of investigators as an important immunosuppressive effector of Treg, which exerts its immunoregulatory activity by binding to inhibitory FcγRIIB receptors expressed on antigen-presenting cells including dendritic cells, endothelial cells, and B cells. More recently, it has been suggested that FGL2 accounts for the immunosuppressive activity of a highly suppressive subset of Treg that express T cell immunoreceptor with Ig and ITIM domains (TIGIT). Here we discuss the important role of Treg and FGL2 in preventing alloimmune and autoimmune disease. The FGL2–FcγRIIB pathway is also known to be utilized by viruses and tumor cells to evade immune surveillance. Moving forward, therapies based on modulation of the FGL2–FcγRIIB pathway hold promise for the treatment of a wide variety of conditions ranging from autoimmunity to cancer.
Highlights
Binding of fibrinogen to its receptor MAC-1 expressed on macrophages leads to macrophage activation, and ligation to TLR4 leads to expression of MCP1.36 The secreted form of Fibrinogen-like protein 2 (FGL2) is known to be produced by CD4+ and CD8+ T cells[25] and is highly expressed by CD4+CD25+Foxp3+ regulatory T cells (Treg).[10,13,37]
We have reported that binding of FGL2 to FcγRIIB on B cells leads to B cell apoptosis and that A20IIA1.6 cells, which lack FcγRIIB, are protected from FGL2-induced apoptosis.[41]
We showed that T effector cells from fgl2Tg mice were hypoproliferative and unable to induce colitis when injected into Rag1-/- mice
Summary
Role of Regulatory T Cells (Treg) and the Treg Effector Molecule Fibrinogenlike Protein 2 in Alloimmunity and Autoimmunity. Andrzej Chruscinski, M.D., Ph.D., Hassan Sadozai, B.Sc., Vanessa RojasLuengas, B.Sc., Agata Bartczak, Ph.D., Ramzi Khattar, M.Sc., Nazia Selzner, M.D., Ph.D., and Gary A. Multi-Organ Transplant Program, University Health Network, University of Toronto, Toronto, Canada
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