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The Fyn–ADAP Axis: Cytotoxicity Versus Cytokine Production in Killer Cells
Lymphocyte signaling cascades responsible for anti-tumor cytotoxicity and inflammatory cytokine production must be tightly regulated in order to control an immune response. Disruption of these cascades can cause immune suppression as seen in a tumor microenvironment, and loss of signaling integrity...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4584950/ https://www.ncbi.nlm.nih.gov/pubmed/26441977 http://dx.doi.org/10.3389/fimmu.2015.00472 |
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author | Gerbec, Zachary J. Thakar, Monica S. Malarkannan, Subramaniam |
author_facet | Gerbec, Zachary J. Thakar, Monica S. Malarkannan, Subramaniam |
author_sort | Gerbec, Zachary J. |
collection | PubMed |
description | Lymphocyte signaling cascades responsible for anti-tumor cytotoxicity and inflammatory cytokine production must be tightly regulated in order to control an immune response. Disruption of these cascades can cause immune suppression as seen in a tumor microenvironment, and loss of signaling integrity can lead to autoimmunity and other forms of host-tissue damage. Therefore, understanding the distinct signaling events that exclusively control specific effector functions of “killer” lymphocytes (T and NK cells) is critical for understanding disease progression and formulating successful immunotherapy. Elucidation of divergent signaling pathways involved in receptor-mediated activation has provided insights into the independent regulation of cytotoxicity and cytokine production in lymphocytes. Specifically, the Fyn signaling axis represents a branch point for killer cell effector functions and provides a model for how cytotoxicity and cytokine production are differentially regulated. While the Fyn–PI(3)K pathway controls multiple functions, including cytotoxicity, cell development, and cytokine production, the Fyn–ADAP pathway preferentially regulates cytokine production in NK and T cells. In this review, we discuss how the structure of Fyn controls its function in lymphocytes and the role this plays in mediating two facets of lymphocyte effector function, cytotoxicity and production of inflammatory cytokines. This offers a model for using mechanistic and structural approaches to understand clinically relevant lymphocyte signaling. |
format | Online Article Text |
id | pubmed-4584950 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-45849502015-10-05 The Fyn–ADAP Axis: Cytotoxicity Versus Cytokine Production in Killer Cells Gerbec, Zachary J. Thakar, Monica S. Malarkannan, Subramaniam Front Immunol Immunology Lymphocyte signaling cascades responsible for anti-tumor cytotoxicity and inflammatory cytokine production must be tightly regulated in order to control an immune response. Disruption of these cascades can cause immune suppression as seen in a tumor microenvironment, and loss of signaling integrity can lead to autoimmunity and other forms of host-tissue damage. Therefore, understanding the distinct signaling events that exclusively control specific effector functions of “killer” lymphocytes (T and NK cells) is critical for understanding disease progression and formulating successful immunotherapy. Elucidation of divergent signaling pathways involved in receptor-mediated activation has provided insights into the independent regulation of cytotoxicity and cytokine production in lymphocytes. Specifically, the Fyn signaling axis represents a branch point for killer cell effector functions and provides a model for how cytotoxicity and cytokine production are differentially regulated. While the Fyn–PI(3)K pathway controls multiple functions, including cytotoxicity, cell development, and cytokine production, the Fyn–ADAP pathway preferentially regulates cytokine production in NK and T cells. In this review, we discuss how the structure of Fyn controls its function in lymphocytes and the role this plays in mediating two facets of lymphocyte effector function, cytotoxicity and production of inflammatory cytokines. This offers a model for using mechanistic and structural approaches to understand clinically relevant lymphocyte signaling. Frontiers Media S.A. 2015-09-16 /pmc/articles/PMC4584950/ /pubmed/26441977 http://dx.doi.org/10.3389/fimmu.2015.00472 Text en Copyright © 2015 Gerbec, Thakar and Malarkannan. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Gerbec, Zachary J. Thakar, Monica S. Malarkannan, Subramaniam The Fyn–ADAP Axis: Cytotoxicity Versus Cytokine Production in Killer Cells |
title | The Fyn–ADAP Axis: Cytotoxicity Versus Cytokine Production in Killer Cells |
title_full | The Fyn–ADAP Axis: Cytotoxicity Versus Cytokine Production in Killer Cells |
title_fullStr | The Fyn–ADAP Axis: Cytotoxicity Versus Cytokine Production in Killer Cells |
title_full_unstemmed | The Fyn–ADAP Axis: Cytotoxicity Versus Cytokine Production in Killer Cells |
title_short | The Fyn–ADAP Axis: Cytotoxicity Versus Cytokine Production in Killer Cells |
title_sort | fyn–adap axis: cytotoxicity versus cytokine production in killer cells |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4584950/ https://www.ncbi.nlm.nih.gov/pubmed/26441977 http://dx.doi.org/10.3389/fimmu.2015.00472 |
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