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Canonical and Non-Canonical Wnt Signaling in Immune Cells

2018; Elsevier BV; Volume: 39; Issue: 10 Linguagem: Inglês

10.1016/j.it.2018.08.006

1471-4981

Wook‐Jin Chae, Alfred L.M. Bothwell,

Cancer-related gene regulation

Wnt ligands are important in inducing crucial functions in cell proliferation, differentiation, apoptosis, motility, and survival. Wnt ligands and their signaling pathways are therefore important for tissue repair and immune responses. T cell development and peripheral immune responses of T cells are highly dependent on Wnt pathway components TCF-1 and β-catenin. The importance of canonical Wnt signaling must be interpreted with caution depending on different microenvironments. Both canonical and non-canonical Wnt pathways appear to be important for macrophage-mediated tissue injury and repair in major organs (e.g., heart). Wnt antagonists such as DKK-1 can harbor immunomodulatory functions that are often β-catenin-independent. Cell differentiation, proliferation, and death are vital for immune homeostasis. Wnt signaling plays essential roles in processes across species. The roles of Wnt signaling proteins and Wnt ligands have been studied in the past, but the context-dependent mechanisms and functions of these pathways in immune responses remain unclear. Recent findings regarding the role of Wnt ligands and Wnt signaling in immune cells and their immunomodulatory mechanisms suggest that Wnt ligands and signaling are significant in regulating immune responses. We introduce recent key findings and future perspectives on Wnt ligands and their signaling pathways in immune cells as well as the immunological roles and functions of Wnt antagonists. Cell differentiation, proliferation, and death are vital for immune homeostasis. Wnt signaling plays essential roles in processes across species. The roles of Wnt signaling proteins and Wnt ligands have been studied in the past, but the context-dependent mechanisms and functions of these pathways in immune responses remain unclear. Recent findings regarding the role of Wnt ligands and Wnt signaling in immune cells and their immunomodulatory mechanisms suggest that Wnt ligands and signaling are significant in regulating immune responses. We introduce recent key findings and future perspectives on Wnt ligands and their signaling pathways in immune cells as well as the immunological roles and functions of Wnt antagonists. CD4+ T cells that are present in the periphery within B cell follicles of secondary lymphoid organs such as lymph nodes and spleen. They are identified by the expression of CXCR5. Tfh cells are important to form and to maintain germinal centers (GCs) via the secretion of IL-21 and IL-4, and the expression of CD40L. CD4+ regulatory T cells (Treg cells) that are found in the GC after immunization with protein antigens. They share phenotypic characteristics with Tfh and Treg cells but are distinct from the two subsets. Tfr cells originate from thymic (t)Treg precursors, not naïve or Tfh cells. They limit Tfh cell and germinal B cell numbers in vivo. a disease caused by infection with Leishmania parasites. It is categorized as a neglected tropical disease and is spread by the bite of phlebotomine sand flies. Typically, there are two forms of leishmaniasis depending on the site of infection. One is cutaneous leishmaniasis in skin and the other is visceral leishmaniasis in internal organs such as spleen, liver and bone marrow. by convention, macrophages are divided into three groups: M2a, M2b, and M2c. M2a macrophages are connected with Th2 cell-mediated immune responses and they produce IL-4. M2b macrophages are stimulated by immune complexes and TLRs. They produce IL-10 and their antigen presentation is upregulated. M2c macrophages secrete IL-10 and TGF-β. They contribute to extracellular matrix components production and tissue remodeling. a mouse breast cancer metastasis model in which the long terminal repeat (LTR) of mouse mammary tumor virus (MMTR) drives mammary gland-specific expression of polyoma virus middle-T antigen. immune cells from the bone marrow-derived myeloid lineage. MDSCs are heterogeneous, immunosuppressive cell type that expand in pathological inflammation such as cancer via an altered hematopoiesis. is a signaling pathway to regulate T cells. Programmed cell death protein (PD)-1 is a coinhibitory ‘checkpoint’ molecule, and is induced upon T cell activation. PD-1 plays an essential role in balancing immune homeostasis and tolerance, but its expression can limit protective immunity and immunosurveillance against tumors. a subset of the CD4+ T cell population that suppress inflammation. Tregs express a lineage-specification transcriptional factor Foxp3, and play a key role to maintain immunological homeostasis in autoimmunity. a transcriptional factor and chromatin organizer that integrates higher-order chromatin architecture for gene expression regulation. both long and short isoforms of TCF-1 possess a high mobility group (HMG) DNA-binding domain and a HDAC domain. Only the TCF-1 long isoforms (p45 and p42) contain an N-terminal β-catenin-binding domain to interact with the protein, whereas the TCF-1 short isoforms (p33 and p30) lack this domain. a pathway mediated by TLRs which play key roles in innate immune responses. TLRs recognize structurally conserved molecules such as PAMP (pathogen-associated molecular patterns) from microbes. these are mediated by Th1 cells (expressing type 1 cytokine IFN-γ) and Th17 cells (expressing cytokine IL-17). Th1/Th17 responses are involved in autoimmunity, pathogen infection and cancer. a subset of differentiated naïve CD4+ T cells that express type 2 cytokines such as IL-4, IL-5, and IL-13, and which play a major role in type 2 inflammation. Th2 cell-mediated responses are important for helminth infections, allergic inflammation, and tissue injury and repair.