Role of Regulatory T Cells (Treg) and the Treg Effector Molecule Fibrinogen-like Protein 2 in Alloimmunity and Autoimmunity

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.

Identification of Novel CD4+ T Cell Subsets in the Target Tissue of Sjögren’s Syndrome and Their Differential Regulation by the Lymphotoxin/LIGHT Signaling Axis

“…Thus, understanding how LGT-resident eTregs suppress self-reactive T cell clones in the target tissue will be an important question to address. The transcriptional signatures derived in this study point to new molecular candidates: Areg, a ligand for EGFR that stimulates Treg-suppressive functions (39) and was recently demonstrated to have a key role in Treg-mediated tissue repair (40); Fgl2, a secreted factor with potent immunoregulatory properties (41); or Itgb8, which is required for the activation of latent TGF-b in Tregs (42).…”

Polymorphisms in TIM-3 and breast cancer susceptibility in Chinese women: A case-control study

“…Individuals using long-term immunosuppressive medications (azathioprine, cyclophosphamide, and cyclosporine) or those with underlying immunologic abnormalities, such as an autoimmune disease or viral infection, are particularly at risk of malignancy [25]. Immune dysregulation plays a vital role in both initiation and progression of autoimmune disease [26]. The evidence indicates that immune suppression contributes to cancer progression.…”

Elevated fibrinogen-like protein 2 in TNBS-induced colitis mice: Association with Th17 and regulatory T cells

“…overexpressed in patients with IBD (1). Additionally, fibrinogen-like protein 2 (FGL2) is one of the immunosuppressive cytokines expressed by Treg cells and has been identified to be an important effector molecule by which Treg cells exerts their immunosuppressive effects (17)(18)(19)(20). FGL2 has been demonstrated to inhibit the proliferation of T cells and the maturation of bone marrow-derived cells.…”

“…FGL2 has been demonstrated to inhibit the proliferation of T cells and the maturation of bone marrow-derived cells. Previous studies have demonstrated that subsets of Treg cells with increased levels of FGL2 are more suppressive and that Treg cells from FGL2 -/mice have been observed exhibit decreased suppressive activity (17,20,21). It was previously identified that the expression of FGL2 in intestinal mucosal biopsies and periphe ral blood was increased in patients with active disease, and decreased in inactive disease.…”