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Inhibition of Allograft Inflammatory Factor-1 in Dendritic Cells Restrains CD4(+) T Cell Effector Responses and Induces CD25(+)Foxp3(+) T Regulatory Subsets
Allograft inflammatory factor-1 (AIF1) is a cytoplasmic scaffold protein shown to influence immune responses in macrophages and microglial cells. The protein contains Ca(2+) binding EF-hand and PDZ interaction domains important for mediating intracellular signaling complexes. This study now reports...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5682305/ https://www.ncbi.nlm.nih.gov/pubmed/29167673 http://dx.doi.org/10.3389/fimmu.2017.01502 |
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author | Elizondo, Diana M. Andargie, Temesgen E. Yang, Dazhi Kacsinta, Apollo D. Lipscomb, Michael W. |
author_facet | Elizondo, Diana M. Andargie, Temesgen E. Yang, Dazhi Kacsinta, Apollo D. Lipscomb, Michael W. |
author_sort | Elizondo, Diana M. |
collection | PubMed |
description | Allograft inflammatory factor-1 (AIF1) is a cytoplasmic scaffold protein shown to influence immune responses in macrophages and microglial cells. The protein contains Ca(2+) binding EF-hand and PDZ interaction domains important for mediating intracellular signaling complexes. This study now reports that AIF1 is expressed in CD11c(+) dendritic cells (DC) and silencing of expression restrains induction of antigen-specific CD4(+) T cell effector responses. AIF1 knockdown in murine DC resulted in impaired T cell proliferation and skewed polarization away from T helper type 1 and 17 fates. In turn, there was a parallel expansion of IL-10-producing and CD25(+)Foxp3(+) T regulatory subsets. These studies are the first to demonstrate that AIF1 expression in DC serves as a potent governor of cognate T cell responses and presents a novel target for engineering tolerogenic DC-based immunotherapies. |
format | Online Article Text |
id | pubmed-5682305 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-56823052017-11-22 Inhibition of Allograft Inflammatory Factor-1 in Dendritic Cells Restrains CD4(+) T Cell Effector Responses and Induces CD25(+)Foxp3(+) T Regulatory Subsets Elizondo, Diana M. Andargie, Temesgen E. Yang, Dazhi Kacsinta, Apollo D. Lipscomb, Michael W. Front Immunol Immunology Allograft inflammatory factor-1 (AIF1) is a cytoplasmic scaffold protein shown to influence immune responses in macrophages and microglial cells. The protein contains Ca(2+) binding EF-hand and PDZ interaction domains important for mediating intracellular signaling complexes. This study now reports that AIF1 is expressed in CD11c(+) dendritic cells (DC) and silencing of expression restrains induction of antigen-specific CD4(+) T cell effector responses. AIF1 knockdown in murine DC resulted in impaired T cell proliferation and skewed polarization away from T helper type 1 and 17 fates. In turn, there was a parallel expansion of IL-10-producing and CD25(+)Foxp3(+) T regulatory subsets. These studies are the first to demonstrate that AIF1 expression in DC serves as a potent governor of cognate T cell responses and presents a novel target for engineering tolerogenic DC-based immunotherapies. Frontiers Media S.A. 2017-11-08 /pmc/articles/PMC5682305/ /pubmed/29167673 http://dx.doi.org/10.3389/fimmu.2017.01502 Text en Copyright © 2017 Elizondo, Andargie, Yang, Kacsinta and Lipscomb. 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 Elizondo, Diana M. Andargie, Temesgen E. Yang, Dazhi Kacsinta, Apollo D. Lipscomb, Michael W. Inhibition of Allograft Inflammatory Factor-1 in Dendritic Cells Restrains CD4(+) T Cell Effector Responses and Induces CD25(+)Foxp3(+) T Regulatory Subsets |
title | Inhibition of Allograft Inflammatory Factor-1 in Dendritic Cells Restrains CD4(+) T Cell Effector Responses and Induces CD25(+)Foxp3(+) T Regulatory Subsets |
title_full | Inhibition of Allograft Inflammatory Factor-1 in Dendritic Cells Restrains CD4(+) T Cell Effector Responses and Induces CD25(+)Foxp3(+) T Regulatory Subsets |
title_fullStr | Inhibition of Allograft Inflammatory Factor-1 in Dendritic Cells Restrains CD4(+) T Cell Effector Responses and Induces CD25(+)Foxp3(+) T Regulatory Subsets |
title_full_unstemmed | Inhibition of Allograft Inflammatory Factor-1 in Dendritic Cells Restrains CD4(+) T Cell Effector Responses and Induces CD25(+)Foxp3(+) T Regulatory Subsets |
title_short | Inhibition of Allograft Inflammatory Factor-1 in Dendritic Cells Restrains CD4(+) T Cell Effector Responses and Induces CD25(+)Foxp3(+) T Regulatory Subsets |
title_sort | inhibition of allograft inflammatory factor-1 in dendritic cells restrains cd4(+) t cell effector responses and induces cd25(+)foxp3(+) t regulatory subsets |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5682305/ https://www.ncbi.nlm.nih.gov/pubmed/29167673 http://dx.doi.org/10.3389/fimmu.2017.01502 |
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