IL-25 exacerbates autoimmune aortitis in IL-1 receptor antagonist-deficient mice.
Sci Rep
; 9(1): 17067, 2019 11 19.
Article
en En
| MEDLINE
| ID: mdl-31745167
ABSTRACT
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-1ß 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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Aortitis
/
Enfermedades Autoinmunes
/
Interleucinas
/
Proteína Antagonista del Receptor de Interleucina 1
Límite:
Animals
Idioma:
En
Revista:
Sci Rep
Año:
2019
Tipo del documento:
Article
País de afiliación:
Japón