CD8+CD103+ iTregs inhibit the progression of lupus nephritis by attenuating glomerular endothelial cell injury.
Rheumatology (Oxford)
; 58(11): 2039-2050, 2019 11 01.
Article
en En
| MEDLINE
| ID: mdl-31329981
OBJECTIVES: We previously reported that ex vivo TGF-ß and IL-2-induced CD8+CD103+ regulatory T cells (CD8+CD103+ iTregs) displayed similar immunosuppressive effect and therapeutic function on lupus mice nephritis to that of CD4+Foxp3+ Tregs. In view of the important role of glomerular endothelial cell (GEC) injury in inflammatory processes in SLE, this study aimed to investigate the nature and mechanism of CD8+CD103+ iTregs-mediated amelioration of LN by attenuating GEC injury. METHODS: Treg cells from patients with SLE and from healthy controls were characterized by flow cytometry analysis. The expression of pro-inflammatory mediators and VEGF were analysed in healthy controls, patients with SLE and MRL/lpr mice by ELISA, western blot, and real-time quantitative RT-PCR (qRT-PCR). Typical lesions of diffuse proliferative LN were observed in MRL/lpr mice through the use of haematoxylin and eosin, Masson, periodic acid-Schiff, periodic acid-Schiff methenamine, transmission electron microscopy and IF microscopy. Angiogenesis was analysed in GECs by cell investigating proliferation, migration, and tube formation. RESULTS: The results revealed that the frequency of Treg cells was inversely correlated with the expression of VCAM-1 and ICAM-1 in patients with SLE. Furthermore, adoptive transfer of CD8+CD103+ iTregs to MRL/lpr mice was associated with decreased levels of autoantibodies and proteinuria, reduced renal pathological lesions, and lowered renal deposition of IgG/C3. We further found that CD8+CD103+ iTregs not only suppressed the expression of pro-inflammatory mediators but also attenuated GEC injury by promoting angiogenesis. CONCLUSION: Our study has identified the role of CD8+CD103+ iTregs on attenuating GEC injury and provided a possible application of this new iTregs subset in lupus nephritis and other autoimmune diseases.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Nefritis Lúpica
/
Antígenos CD
/
Linfocitos T Reguladores
/
Linfocitos T CD8-positivos
/
Cadenas alfa de Integrinas
/
Células Endoteliales
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Rheumatology (Oxford)
Asunto de la revista:
REUMATOLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Reino Unido