Immunomodulatory effects of umbilical mesenchymal stem cell-derived exosomes on CD4+ T cells in patients with primary Sjögren's syndrome

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-β 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.

Exosomes in Action: Unraveling Their Role in Autoimmune Diseases and Exploring Potential Therapeutic Applications

“…The occurrence of disease is promoted due to an imbalance between the number of Treg cells and the number of Th17 cells when compared to the healthy control. Other studies have also found that ( 54 ) human umbilical cord mesenchymal stem cell-derived exosomes can inhibit abnormal proliferation of CD4 + T cells and their apoptosis. They can also regulate the balance of Th17 and Treg cell numbers, suppress the secretion of pro-inflammatory factors like IFN-γ, TNF-α, IL-6, IL-17A, as well as IL-17F from CD4 + T cells and induce the secretion of anti-inflammatory factors like IL-10 and TGF-β.…”

New genetic insights into immunotherapy outcomes in gastric cancer via single-cell RNA sequencing and random forest model

“…Post-enrichment, the cells were processed through centrifugation over a non-continuous Percoll gradient, specifically layering a 40% Percoll solution atop an 80% solution and centrifuging at 320 g for 25 min. The purified cells were then propagated in RPMI 1640 medium, enriched with 10% FBS, 1% antibiotics, 10 mM HEPES, 2 mM L-glutamine, 1 mM sodium pyruvate, MEM non-essential amino acids, and 55 μM β-mercaptoethanol [ 31 , 32 ].…”

Advances in the application of extracellular vesicles derived from three-dimensional culture of stem cells

“…Here we present 3D culture of umbilical cord-derived SCs, mainly UCMSCs and umbilical cord blood MSCs (UCBMSCs). Similar to BMMSC-EVs, EVs derived from 2D cultured UCMSCs have been found to exert protective effects in various ways, such as acute and chronic renal injury, heart injury, liver injury, brain injury, and immunomodulation, as well as alleviation of type 2 diabetes mellitus [ 23 , 173 – 179 ]. As with BMMSCs, in an in vivo wound healing model, EVs derived from 3D spheroid culture and 3D spinner flask culture of UCMSCs were able to promote epithelialization of wounds and accelerate post-injury skin healing, with a more dramatic effect than 2D-EVs [ 147 , 163 ].…”