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IL-23p19 and CD5 antigen-like form a possible novel heterodimeric cytokine and contribute to experimental autoimmune encephalomyelitis development
Among various cytokines, interleukin (IL)-12 family cytokines have very unique characteristics in that they are composed of two distinct subunits and these subunits are shared with each other. IL-23, one of the IL-12 family cytokines, consists of p19 and p40 subunits, is mainly produced by antigen-p...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933155/ https://www.ncbi.nlm.nih.gov/pubmed/33664371 http://dx.doi.org/10.1038/s41598-021-84624-9 |
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author | Hasegawa, Hideaki Mizoguchi, Izuru Orii, Naoko Inoue, Shinya Katahira, Yasuhiro Yoneto, Toshihiko Xu, Mingli Miyazaki, Toru Yoshimoto, Takayuki |
author_facet | Hasegawa, Hideaki Mizoguchi, Izuru Orii, Naoko Inoue, Shinya Katahira, Yasuhiro Yoneto, Toshihiko Xu, Mingli Miyazaki, Toru Yoshimoto, Takayuki |
author_sort | Hasegawa, Hideaki |
collection | PubMed |
description | Among various cytokines, interleukin (IL)-12 family cytokines have very unique characteristics in that they are composed of two distinct subunits and these subunits are shared with each other. IL-23, one of the IL-12 family cytokines, consists of p19 and p40 subunits, is mainly produced by antigen-presenting cells, and plays a critical role in the expansion and maintenance of pathogenic helper CD4(+) T (Th)17 cells. Since we initially found that p19 is secreted in the culture supernatant of activated CD4(+) T cells, we have further investigated the role of p19. p19 was revealed to associate with CD5 antigen-like (CD5L), which is a repressor of Th17 pathogenicity and is highly expressed in non-pathogenic Th17 cells, to form a composite p19/CD5L. This p19/CD5L was shown to activate STAT5 and enhance the differentiation into granulocyte macrophage colony-stimulating factor (GM-CSF)-producing CD4(+) T cells. Both CD4(+) T cell-specific conditional p19-deficient mice and complete CD5L-deficient mice showed significantly alleviated experimental autoimmune encephalomyelitis (EAE) with reduced frequency of GM-CSF(+)CD4(+) T cells. During the course of EAE, the serum level of p19/CD5L, but not CD5L, correlated highly with the clinical symptoms. Thus, the composite p19/CD5L is a possible novel heterodimeric cytokine that contributes to EAE development with GM-CSF up-regulation. |
format | Online Article Text |
id | pubmed-7933155 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-79331552021-03-05 IL-23p19 and CD5 antigen-like form a possible novel heterodimeric cytokine and contribute to experimental autoimmune encephalomyelitis development Hasegawa, Hideaki Mizoguchi, Izuru Orii, Naoko Inoue, Shinya Katahira, Yasuhiro Yoneto, Toshihiko Xu, Mingli Miyazaki, Toru Yoshimoto, Takayuki Sci Rep Article Among various cytokines, interleukin (IL)-12 family cytokines have very unique characteristics in that they are composed of two distinct subunits and these subunits are shared with each other. IL-23, one of the IL-12 family cytokines, consists of p19 and p40 subunits, is mainly produced by antigen-presenting cells, and plays a critical role in the expansion and maintenance of pathogenic helper CD4(+) T (Th)17 cells. Since we initially found that p19 is secreted in the culture supernatant of activated CD4(+) T cells, we have further investigated the role of p19. p19 was revealed to associate with CD5 antigen-like (CD5L), which is a repressor of Th17 pathogenicity and is highly expressed in non-pathogenic Th17 cells, to form a composite p19/CD5L. This p19/CD5L was shown to activate STAT5 and enhance the differentiation into granulocyte macrophage colony-stimulating factor (GM-CSF)-producing CD4(+) T cells. Both CD4(+) T cell-specific conditional p19-deficient mice and complete CD5L-deficient mice showed significantly alleviated experimental autoimmune encephalomyelitis (EAE) with reduced frequency of GM-CSF(+)CD4(+) T cells. During the course of EAE, the serum level of p19/CD5L, but not CD5L, correlated highly with the clinical symptoms. Thus, the composite p19/CD5L is a possible novel heterodimeric cytokine that contributes to EAE development with GM-CSF up-regulation. Nature Publishing Group UK 2021-03-04 /pmc/articles/PMC7933155/ /pubmed/33664371 http://dx.doi.org/10.1038/s41598-021-84624-9 Text en © The Author(s) 2021, corrected publication 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Hasegawa, Hideaki Mizoguchi, Izuru Orii, Naoko Inoue, Shinya Katahira, Yasuhiro Yoneto, Toshihiko Xu, Mingli Miyazaki, Toru Yoshimoto, Takayuki IL-23p19 and CD5 antigen-like form a possible novel heterodimeric cytokine and contribute to experimental autoimmune encephalomyelitis development |
title | IL-23p19 and CD5 antigen-like form a possible novel heterodimeric cytokine and contribute to experimental autoimmune encephalomyelitis development |
title_full | IL-23p19 and CD5 antigen-like form a possible novel heterodimeric cytokine and contribute to experimental autoimmune encephalomyelitis development |
title_fullStr | IL-23p19 and CD5 antigen-like form a possible novel heterodimeric cytokine and contribute to experimental autoimmune encephalomyelitis development |
title_full_unstemmed | IL-23p19 and CD5 antigen-like form a possible novel heterodimeric cytokine and contribute to experimental autoimmune encephalomyelitis development |
title_short | IL-23p19 and CD5 antigen-like form a possible novel heterodimeric cytokine and contribute to experimental autoimmune encephalomyelitis development |
title_sort | il-23p19 and cd5 antigen-like form a possible novel heterodimeric cytokine and contribute to experimental autoimmune encephalomyelitis development |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933155/ https://www.ncbi.nlm.nih.gov/pubmed/33664371 http://dx.doi.org/10.1038/s41598-021-84624-9 |
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