Human umbilical cord mesenchymal stem cells improve disease characterization of Sjogren's syndrome in NOD mice through regulation of gut microbiota and Treg/Th17 cellular immunity.
Immun Inflamm Dis
; 12(1): e1139, 2024 Jan.
Article
en En
| MEDLINE
| ID: mdl-38270310
ABSTRACT
BACKGROUND:
For the unclear pathogenesis of Sjogren's syndrome (SS), further exploration is necessary. Mesenchymal stem cells (MSCs) and derived exosomes (MSCs-exo) have exhibited promising results in treating SS. OBJECT This study aimed to investigate the effect and mechanism of human umbilical cord MSCs (UC-MSCs) on SS.METHODS:
Nonobese Diabetic (NOD) mouse splenic T cells were co-cultured with UC-MSCs and UC-MSCs-exo, and interferon-gamma (IFN-γ), interleukin (IL)-6, IL-10, prostaglandin E2 (PGE2), and transforming growth factor-ß1 (TGF-ß1) levels in the supernatant were assessed by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Co-cultured T cells were injected into NOD mice via the tail vein. The inflammatory cell infiltration in the intestine and the submandibular gland was characterized by hematoxylin-eosin staining. Treg/Th17 homeostasis within the spleen was determined by flow cytometry. Gut microbiota was detected by 16S rRNA sequencing, and the relationship between differential microbiota and Treg/Th17 cytokines was analyzed by the Pearson correlation coefficient.RESULTS:
UC-MSCs, UC-MSCs-exo, and NOD mouse splenic T cells were successfully cultured and identified. After T cells were co-cultured with UC-MSCs and UC-MSCs-exo, both IFN-γ and IL-6 were decreased while IL-10, PGE2, and TGF-ß1 were increased in transcriptional and translational levels. UC-MSCs and UC-MSCs-exo partially restored salivary secretion function, reduced Ro/SSA antibody and α-Fodrin immunoglobulin A levels, reduced inflammatory cell infiltration in the intestine and submandibular gland, raised proportion of Treg cells, decreased IFN-γ, IL-6, IL-2, IL-17, lipopolysaccharide, and tumor necrosis factor-alpha levels, and raised IL-10, Foxp3, and TGF-ß1 levels by affecting co-cultured T cells. The intervention of UC-MSCs and UC-MSCs-exo improved intestinal homeostasis in NOD mice by increasing microbiota diversity and richness. Additionally, differential microbiota was significantly associated with Treg/Th17 cytokine levels.CONCLUSION:
Human UC-MSCs and UC-MSCs-exo improved disease characterization of SS in NOD mice through regulation of gut microbiota and Treg/Th17 cellular immunity.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Síndrome de Sjögren
/
Células Madre Mesenquimatosas
/
Microbioma Gastrointestinal
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Immun Inflamm Dis
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Reino Unido