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 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
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| Enthalten in: |
Scientific reports - 9(2019), 1 vom: 19. Nov., Seite 17067 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yoshizaki, Takamichi [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 03.11.2020 Date Revised 10.01.2021 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41598-019-53633-0 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM303481560 |
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| 100 | 1 | |a Yoshizaki, Takamichi |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a IL-25 exacerbates autoimmune aortitis in IL-1 receptor antagonist-deficient mice |
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| 520 | |a 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 | ||
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| 700 | 1 | |a Itoh, Satoshi |e verfasserin |4 aut | |
| 700 | 1 | |a Yamaguchi, Sachiko |e verfasserin |4 aut | |
| 700 | 1 | |a Numata, Takafumi |e verfasserin |4 aut | |
| 700 | 1 | |a Nambu, Aya |e verfasserin |4 aut | |
| 700 | 1 | |a Kimura, Naoyuki |e verfasserin |4 aut | |
| 700 | 1 | |a Suto, Hajime |e verfasserin |4 aut | |
| 700 | 1 | |a Okumura, Ko |e verfasserin |4 aut | |
| 700 | 1 | |a Sudo, Katsuko |e verfasserin |4 aut | |
| 700 | 1 | |a Yamaguchi, Atsushi |e verfasserin |4 aut | |
| 700 | 1 | |a Nakae, Susumu |e verfasserin |4 aut | |
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