Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Major histocompatibility complex (MHC) class II molecules expressed on monocytes may play a role in the control of differentiation of antigen-presenting cells. A soluble LAG-3 (CD223) molecule (sLAG-3) is a natural, high-affinity ligand for MHC class II. It is known to induce maturation of monocyte-derived dendritic cells in vitro and is used as a vaccine adjuvant to induce CD4 T helper type 1 responses and CD8 T-cell responses in vivo. Here, we demonstrate that sLAG-3 (but not an MHC class II-specific monoclonal antibody) reduces the differentiation of monocytes into macrophages in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) as well as their differentiation into dendritic cells in the presence of GM-CSF and interleukin-4, as shown by a decrease in CD14 and CD1a expression, respectively. Dendritic cells derived from monocytes in the presence of sLAG-3 showed impaired antigen-presentation function, as assessed by the reduced capability to induce proliferation of T cells. Our results suggest that activated LAG-3(+) lymphocytes present at sites of inflammation may reduce the differentiation of monocytes into macrophages or fully competent antigen-presenting dendritic cells, thus limiting the magnitude of the ongoing T-cell immune responses.
 ...
PMID:LAG-3 (CD223) reduces macrophage and dendritic cell differentiation from monocyte precursors. 1572 Apr 38

Galectin-3 is a 31-kDa lectin that modulates T-cell responses through several mechanisms, including apoptosis, T-cell receptor (TCR) cross-linking, and TCR downregulation. We found that patients with pancreatic ductal adenocarcinoma (PDA) who responded to a granulocyte-macrophage colony-stimulating factor-secreting allogeneic PDA vaccine developed neutralizing antibodies to galectin-3 after immunization. We show that galectin-3 binds activated antigen-committed CD8(+) T cells only in the tumor microenvironment. Galectin-3-deficient mice exhibit improved CD8(+) T-cell effector function and increased expression of several inflammatory genes. Galectin-3 binds to LAG-3, and LAG-3 expression is necessary for galectin-3-mediated suppression of CD8(+) T cells in vitro. Lastly, galectin-3-deficient mice have elevated levels of circulating plasmacytoid dendritic cells, which are superior to conventional dendritic cells in activating CD8(+) T cells. Thus, inhibiting galectin-3 in conjunction with CD8(+) T-cell-directed immunotherapies should enhance the tumor-specific immune response.
 ...
PMID:Galectin-3 Shapes Antitumor Immune Responses by Suppressing CD8+ T Cells via LAG-3 and Inhibiting Expansion of Plasmacytoid Dendritic Cells. 2569 28