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Autoantibodies to Chemokines and Cytokines Participate in the Regulation of Cancer and Autoimmunity

We have previously shown that predominant expression of key inflammatory cytokines and chemokines at autoimmune sites or tumor sites induces loss of B cells tolerance, resulting in autoantibody production against the dominant cytokine/chemokine that is largely expressed at these sites. These autoant...

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Detalles Bibliográficos
Autor principal: Karin, Nathan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5884937/
https://www.ncbi.nlm.nih.gov/pubmed/29651292
http://dx.doi.org/10.3389/fimmu.2018.00623
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author Karin, Nathan
author_facet Karin, Nathan
author_sort Karin, Nathan
collection PubMed
description We have previously shown that predominant expression of key inflammatory cytokines and chemokines at autoimmune sites or tumor sites induces loss of B cells tolerance, resulting in autoantibody production against the dominant cytokine/chemokine that is largely expressed at these sites. These autoantibodies are high-affinity neutralizing antibodies. Based on animal models studies, we suggested that they participate in the regulation of cancer and autoimmunity, albeit at the level of their production cannot entirely prevent the development and progression of these diseases. We have, therefore, named this selective breakdown of tolerance as “Beneficial Autoimmunity.” Despite its beneficial outcome, this process is likely to be stochastic and not directed by a deterministic mechanism, and is likely to be associated with the dominant expression of these inflammatory mediators at sites that are partially immune privileged. A recent study conducted on autoimmune regulator-deficient patients reported that in human this type of breakdown of B cell tolerance is T cell dependent. This explains, in part, why the response is highly restricted, and includes high-affinity antibodies. The current mini-review explores this subject from different complementary perspectives. It also discusses three optional translational aspects: amplification of autoantibody production as a therapeutic approach, development of autoantibody based diagnostic tools, and the use of B cells from donors that produce these autoantibodies for the development of high-affinity human monoclonal antibodies.
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spelling pubmed-58849372018-04-12 Autoantibodies to Chemokines and Cytokines Participate in the Regulation of Cancer and Autoimmunity Karin, Nathan Front Immunol Immunology We have previously shown that predominant expression of key inflammatory cytokines and chemokines at autoimmune sites or tumor sites induces loss of B cells tolerance, resulting in autoantibody production against the dominant cytokine/chemokine that is largely expressed at these sites. These autoantibodies are high-affinity neutralizing antibodies. Based on animal models studies, we suggested that they participate in the regulation of cancer and autoimmunity, albeit at the level of their production cannot entirely prevent the development and progression of these diseases. We have, therefore, named this selective breakdown of tolerance as “Beneficial Autoimmunity.” Despite its beneficial outcome, this process is likely to be stochastic and not directed by a deterministic mechanism, and is likely to be associated with the dominant expression of these inflammatory mediators at sites that are partially immune privileged. A recent study conducted on autoimmune regulator-deficient patients reported that in human this type of breakdown of B cell tolerance is T cell dependent. This explains, in part, why the response is highly restricted, and includes high-affinity antibodies. The current mini-review explores this subject from different complementary perspectives. It also discusses three optional translational aspects: amplification of autoantibody production as a therapeutic approach, development of autoantibody based diagnostic tools, and the use of B cells from donors that produce these autoantibodies for the development of high-affinity human monoclonal antibodies. Frontiers Media S.A. 2018-03-29 /pmc/articles/PMC5884937/ /pubmed/29651292 http://dx.doi.org/10.3389/fimmu.2018.00623 Text en Copyright © 2018 Karin. https://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) and the copyright owner 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
Karin, Nathan
Autoantibodies to Chemokines and Cytokines Participate in the Regulation of Cancer and Autoimmunity
title Autoantibodies to Chemokines and Cytokines Participate in the Regulation of Cancer and Autoimmunity
title_full Autoantibodies to Chemokines and Cytokines Participate in the Regulation of Cancer and Autoimmunity
title_fullStr Autoantibodies to Chemokines and Cytokines Participate in the Regulation of Cancer and Autoimmunity
title_full_unstemmed Autoantibodies to Chemokines and Cytokines Participate in the Regulation of Cancer and Autoimmunity
title_short Autoantibodies to Chemokines and Cytokines Participate in the Regulation of Cancer and Autoimmunity
title_sort autoantibodies to chemokines and cytokines participate in the regulation of cancer and autoimmunity
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5884937/
https://www.ncbi.nlm.nih.gov/pubmed/29651292
http://dx.doi.org/10.3389/fimmu.2018.00623
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