Role of TNF superfamily ligands in innate immunity

• Published in: Immunologic research Vol. 50; no. 2-3; pp. 159 - 174
• Main Author: Vujanovic, Nikola L.
• Format: Journal Article
• Language: English
• Published: New York Humana Press Inc 01.08.2011; Springer Nature B.V
• Subjects: Allergology; Animals; Apoptosis; Biomedical and Life Sciences; Biomedicine; Cancer; Cells; Cytokines; Cytotoxicity; Dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - immunology; Effector cells; endopeptidase; Gene Expression Regulation - immunology; Granules; Helper cells; Humans; Immune response; Immune system; Immunity, Innate - immunology; Immunologic Factors - metabolism; Immunologic Factors - pharmacology; Immunology; Inflammation; Interleukin-15 - metabolism; Interleukin-15 - pharmacology; Internal Medicine; Killer Cells, Natural - drug effects; Killer Cells, Natural - immunology; Leukemia; Lymphocytes T; Lymphoid tissue; Medicine/Public Health; Natural killer cells; Neoplasms - genetics; Neoplasms - immunology; Neurons; Pathogens; Perforin; Plasma membranes; Polarization; Receptors, Tumor Necrosis Factor - genetics; Receptors, Tumor Necrosis Factor - immunology; Reviews; Serine proteinase; Tumor necrosis factor; Tumor Necrosis Factor-alpha - metabolism; Tumor Necrosis Factor-alpha - pharmacology; Tumor Necrosis Factors - genetics; Tumor Necrosis Factors - immunology; University of Pittsburgh Immunology 2011; TNF superfamily ligands; Cytotoxicity; NK cells; Cross talk; Dendritic cells; TNF superfamily receptors
• ISSN: 0257-277X; 1559-0755
• DOI: 10.1007/s12026-011-8228-8

Natural killer (NK) cells and dendritic cells (DCs) are essential effector cells of the innate immune system that rapidly recognize and eliminate microbial pathogens and abnormal cells, and induce and regulate adaptive immune functions. While NK cells express perforin and granzymes in the lysosomal granules and transmembrane tumor necrosis factor superfamily ligands (tmTNFSFL) on the plasma membrane, DCs express only tmTNFSFL on the plasma membrane. Perforin and granzymes are cytolytic molecules, which NK cells use to mediate a secretory/necrotic killing mechanism against rare leukemia cell targets. TNFSFL are pleiotropic transmembrane molecules, which can mediate a variety of important functions such as apoptosis, development of peripheral lymphoid tissues, inflammation and regulation of immune functions. Using tmTNFSFL, NK cells and DCs mediate a cell contact-dependent non-secretory apoptotic cytotoxic mechanism against virtually all types of cancer cells, and cross talk that leads to polarization and reciprocal stimulation and amplification of Th1 type cytokines secreted by NK cells and DCs. In this paper, we review and discuss the supporting evidence of the non-secretory, tmTNFSFL-mediated innate mechanisms of NK cells and DCs, their roles in anticancer immune defense and potential of their modulation and use in prevention and treatment of cancer.