Immunomodulatory effects of umbilical mesenchymal stem cell-derived exosomes on CD4+ T cells in patients with primary Sjögren's syndrome.
Inflammopharmacology
; 31(4): 1823-1838, 2023 Aug.
Article
en En
| MEDLINE
| ID: mdl-37012581
ABSTRACT
BACKGROUND:
Primary Sjögren's syndrome (pSS) is an autoimmune disease that leads to the destruction of exocrine glands and multisystem lesions. Abnormal proliferation, apoptosis, and differentiation of CD4+ T cells are key factors in the pathogenesis of pSS. Autophagy is one of the important mechanisms to maintain immune homeostasis and function of CD4+ T cells. Human umbilical cord mesenchymal stem cell-derived exosomes (UCMSC-Exos) may simulate the immunoregulation of MSCs while avoiding the risks of MSCs treatment. However, whether UCMSC-Exos can regulate the functions of CD4+ T cells in pSS, and whether the effects via the autophagy pathway remains unclear.METHODS:
The study analyzed retrospectively the peripheral blood lymphocyte subsets in pSS patients, and explored the relationship between lymphocyte subsets and disease activity. Next, peripheral blood CD4+ T cells were sorted using immunomagnetic beads. The proliferation, apoptosis, differentiation, and inflammatory factors of CD4+ T cells were determined using flow cytometry. Autophagosomes of CD4+ T cells were detected using transmission electron microscopy, autophagy-related proteins and genes were detected using western blotting or RT-qPCR.RESULTS:
The study demonstrated that the peripheral blood CD4+ T cells decreased in pSS patients, and negatively correlated with disease activity. UCMSC-Exos inhibited excessive proliferation and apoptosis of CD4+ T cells in pSS patients, blocked them in the G0/G1 phase, inhibited them from entering the S phase, reduced the Th17 cell ratio, elevated the Treg ratio, inhibited IFN-γ, TNF-α, IL-6, IL-17A, and IL-17F secretion, and promoted IL-10 and TGF-ß secretion. UCMSC-Exos reduced the elevated autophagy levels in the peripheral blood CD4+ T cells of patients with pSS. Furthermore, UCMSC-Exos regulated CD4+ T cell proliferation and early apoptosis, inhibited Th17 cell differentiation, promoted Treg cell differentiation, and restored the Th17/Treg balance in pSS patients through the autophagy pathway.CONCLUSIONS:
The study indicated that UCMSC-Exos exerts an immunomodulatory effect on the CD4+ T cells, and maybe as a new treatment for pSS.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Síndrome de Sjögren
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Exosomas
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Células Madre Mesenquimatosas
Tipo de estudio:
Observational_studies
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Risk_factors_studies
Idioma:
En
Revista:
Inflammopharmacology
Asunto de la revista:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Año:
2023
Tipo del documento:
Article