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IL-25 exacerbates autoimmune aortitis in IL-1 receptor antagonist-deficient mice
IL-25, a member of the IL-17 family of cytokines, is known to enhance type 2 immune responses, but suppress type 3 (IL-17A)-mediated immune responses. Mice deficient in IL-1 receptor antagonist (Il1rn(−/−) mice) have excessive IL-1 signaling, resulting in spontaneous development of IL-1–, TNF– and I...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6864066/ https://www.ncbi.nlm.nih.gov/pubmed/31745167 http://dx.doi.org/10.1038/s41598-019-53633-0 |
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author | Yoshizaki, Takamichi Itoh, Satoshi Yamaguchi, Sachiko Numata, Takafumi Nambu, Aya Kimura, Naoyuki Suto, Hajime Okumura, Ko Sudo, Katsuko Yamaguchi, Atsushi Nakae, Susumu |
author_facet | Yoshizaki, Takamichi Itoh, Satoshi Yamaguchi, Sachiko Numata, Takafumi Nambu, Aya Kimura, Naoyuki Suto, Hajime Okumura, Ko Sudo, Katsuko Yamaguchi, Atsushi Nakae, Susumu |
author_sort | Yoshizaki, Takamichi |
collection | PubMed |
description | IL-25, a member of the IL-17 family of cytokines, is known to enhance type 2 immune responses, but suppress type 3 (IL-17A)-mediated immune responses. Mice deficient in IL-1 receptor antagonist (Il1rn(−/−) mice) have excessive IL-1 signaling, resulting in spontaneous development of IL-1–, TNF– and IL-17A–dependent aortitis. We found that expression of II25 mRNA was increased in the aortae of Il1rn(−/−) mice, suggesting that IL-25 may suppress development of IL-1–, TNF– and IL-17A–dependent aortitis in Il1rn(−/−) mice by inhibiting type 3-mediated immune responses. However, we unexpectedly found that Il25(−/−)Il1rn(−/−) mice showed attenuated development of aortitis, accompanied by reduced accumulation of inflammatory cells such as dendritic cells, macrophages and neutrophils and reduced mRNA expression of Il17a and Tnfa—but not Il4 or Il13—in local lesions compared with Il1rn(−/−) mice. Tissue–, but not immune cell–, derived IL-25 was crucial for development of aortitis. IL-25 enhanced IL-1β and TNF production by IL-25 receptor–expressing dendritic cells and macrophages, respectively, at inflammatory sites of aortae of Il1rn(−/−) mice, contributing to exacerbation of development of IL-1–, TNF– and IL-17A–dependent aortitis in those mice. Our findings suggest that neutralization of IL-25 may be a potential therapeutic target for aortitis. |
format | Online Article Text |
id | pubmed-6864066 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-68640662019-12-03 IL-25 exacerbates autoimmune aortitis in IL-1 receptor antagonist-deficient mice Yoshizaki, Takamichi Itoh, Satoshi Yamaguchi, Sachiko Numata, Takafumi Nambu, Aya Kimura, Naoyuki Suto, Hajime Okumura, Ko Sudo, Katsuko Yamaguchi, Atsushi Nakae, Susumu Sci Rep Article IL-25, a member of the IL-17 family of cytokines, is known to enhance type 2 immune responses, but suppress type 3 (IL-17A)-mediated immune responses. Mice deficient in IL-1 receptor antagonist (Il1rn(−/−) mice) have excessive IL-1 signaling, resulting in spontaneous development of IL-1–, TNF– and IL-17A–dependent aortitis. We found that expression of II25 mRNA was increased in the aortae of Il1rn(−/−) mice, suggesting that IL-25 may suppress development of IL-1–, TNF– and IL-17A–dependent aortitis in Il1rn(−/−) mice by inhibiting type 3-mediated immune responses. However, we unexpectedly found that Il25(−/−)Il1rn(−/−) mice showed attenuated development of aortitis, accompanied by reduced accumulation of inflammatory cells such as dendritic cells, macrophages and neutrophils and reduced mRNA expression of Il17a and Tnfa—but not Il4 or Il13—in local lesions compared with Il1rn(−/−) mice. Tissue–, but not immune cell–, derived IL-25 was crucial for development of aortitis. IL-25 enhanced IL-1β and TNF production by IL-25 receptor–expressing dendritic cells and macrophages, respectively, at inflammatory sites of aortae of Il1rn(−/−) mice, contributing to exacerbation of development of IL-1–, TNF– and IL-17A–dependent aortitis in those mice. Our findings suggest that neutralization of IL-25 may be a potential therapeutic target for aortitis. Nature Publishing Group UK 2019-11-19 /pmc/articles/PMC6864066/ /pubmed/31745167 http://dx.doi.org/10.1038/s41598-019-53633-0 Text en © The Author(s) 2019 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Yoshizaki, Takamichi Itoh, Satoshi Yamaguchi, Sachiko Numata, Takafumi Nambu, Aya Kimura, Naoyuki Suto, Hajime Okumura, Ko Sudo, Katsuko Yamaguchi, Atsushi Nakae, Susumu IL-25 exacerbates autoimmune aortitis in IL-1 receptor antagonist-deficient mice |
title | IL-25 exacerbates autoimmune aortitis in IL-1 receptor antagonist-deficient mice |
title_full | IL-25 exacerbates autoimmune aortitis in IL-1 receptor antagonist-deficient mice |
title_fullStr | IL-25 exacerbates autoimmune aortitis in IL-1 receptor antagonist-deficient mice |
title_full_unstemmed | IL-25 exacerbates autoimmune aortitis in IL-1 receptor antagonist-deficient mice |
title_short | IL-25 exacerbates autoimmune aortitis in IL-1 receptor antagonist-deficient mice |
title_sort | il-25 exacerbates autoimmune aortitis in il-1 receptor antagonist-deficient mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6864066/ https://www.ncbi.nlm.nih.gov/pubmed/31745167 http://dx.doi.org/10.1038/s41598-019-53633-0 |
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