| First Author | Yoshizaki T | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 17067 |
| PubMed ID | 31745167 | Mgi Jnum | J:287341 |
| Mgi Id | MGI:6405843 | Doi | 10.1038/s41598-019-53633-0 |
| Citation | Yoshizaki T, et al. (2019) IL-25 exacerbates autoimmune aortitis in IL-1 receptor antagonist-deficient mice. Sci Rep 9(1):17067 |
| abstractText | 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-1beta 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. |
