Gut microbiota differently contributes to intestinal immune phenotype and systemic autoimmune progression in female and male lupus-prone mice.
J Autoimmun
; 108: 102420, 2020 03.
Article
en En
| MEDLINE
| ID: mdl-32019684
ABSTRACT
The risk of developing systemic lupus erythematosus (SLE) is about 9 times higher in women as compared to men. Our recent report, which used (SWRxNZB) F1 (SNF1) mouse model of spontaneous lupus, showed a potential link between immune response initiated in the gut mucosa at juvenile age (sex hormone independent) and SLE susceptibility. Here, using this mouse model, we show that gut microbiota contributes differently to pro-inflammatory immune response in the intestine and autoimmune progression in lupus-prone males and females. We found that gut microbiota composition in male and female littermates are significantly different only at adult ages. However, depletion of gut microbes causes suppression of autoimmune progression only in females. In agreement, microbiota depletion suppressed the pro-inflammatory cytokine response of gut mucosa in juvenile and adult females. Nevertheless, microbiota from females and males showed, upon cross-transfer, contrasting abilities to modulate disease progression. Furthermore, orchidectomy (castration) not only caused changes in the composition of gut microbiota, but also a modest acceleration of autoimmune progression. Overall, our work shows that microbiota-dependent pro-inflammatory immune response in the gut mucosa of females initiated at juvenile ages and androgen-dependent protection of males contribute to gender differences in the intestinal immune phenotype and systemic autoimmune progression.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fenotipo
/
Autoinmunidad
/
Microbioma Gastrointestinal
/
Lupus Eritematoso Sistémico
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Autoimmun
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos