Therapeutic Effect of CD4+CD25+ Regulatory T Cells Amplified In Vitro on Experimental Autoimmune Neuritis in Rats

Wang, Feng Jie; Cui, Dan; Qian, Wei

doi:10.1159/000489919

Cited by 14 publications

(9 citation statements)

References 20 publications

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“…10E). Consistent with prior literature, CD45 + CD3 + CD4 + were considered Helper T cells and CD45 + CD3 + CD4 + CD25 + were considered regulatory T cells (Tregs) [77,78] (Fig. 10F).…”

Section: In Utero Injury Induces Long-term Changes In Peripheral and Central Immune Cell Populationssupporting

confidence: 79%

Sustained peripheral immune hyper-reactivity (SPIHR): an enduring biomarker of altered inflammatory responses in adult rats after perinatal brain injury

Kitase

Chin

Ramachandra

et al. 2021

J Neuroinflammation

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Background Chorioamnionitis (CHORIO) is a principal risk factor for preterm birth and is the most common pathological abnormality found in the placentae of preterm infants. CHORIO has a multitude of effects on the maternal–placental–fetal axis including profound inflammation. Cumulatively, these changes trigger injury in the developing immune and central nervous systems, thereby increasing susceptibility to chronic sequelae later in life. Despite this and reports of neural–immune changes in children with cerebral palsy, the extent and chronicity of the peripheral immune and neuroinflammatory changes secondary to CHORIO has not been fully characterized. Methods We examined the persistence and time course of peripheral immune hyper-reactivity in an established and translational model of perinatal brain injury (PBI) secondary to CHORIO. Pregnant Sprague–Dawley rats underwent laparotomy on embryonic day 18 (E18, preterm equivalent). Uterine arteries were occluded for 60 min, followed by intra-amniotic injection of lipopolysaccharide (LPS). Serum and peripheral blood mononuclear cells (PBMCs) were collected at young adult (postnatal day P60) and middle-aged equivalents (P120). Serum and PBMCs secretome chemokines and cytokines were assayed using multiplex electrochemiluminescent immunoassay. Multiparameter flow cytometry was performed to interrogate immune cell populations. Results Serum levels of interleukin-1β (IL-1β), IL-5, IL-6, C–X–C Motif Chemokine Ligand 1 (CXCL1), tumor necrosis factor-α (TNF-α), and C–C motif chemokine ligand 2/monocyte chemoattractant protein-1 (CCL2/MCP-1) were significantly higher in CHORIO animals compared to sham controls at P60. Notably, CHORIO PBMCs were primed. Specifically, they were hyper-reactive and secreted more inflammatory mediators both at baseline and when stimulated in vitro. While serum levels of cytokines normalized by P120, PBMCs remained primed, and hyper-reactive with a robust pro-inflammatory secretome concomitant with a persistent change in multiple T cell populations in CHORIO animals. Conclusions The data indicate that an in utero inflammatory insult leads to neural–immune changes that persist through adulthood, thereby conferring vulnerability to brain and immune system injury throughout the lifespan. This unique molecular and cellular immune signature including sustained peripheral immune hyper-reactivity (SPIHR) and immune cell priming may be a viable biomarker of altered inflammatory responses following in utero insults and advances our understanding of the neuroinflammatory cascade that leads to perinatal brain injury and later neurodevelopmental disorders, including cerebral palsy.

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“…10E). Consistent with prior literature, CD45 + CD3 + CD4 + were considered Helper T cells and CD45 + CD3 + CD4 + CD25 + were considered regulatory T cells (Tregs) [77,78] (Fig. 10F).…”

Section: In Utero Injury Induces Long-term Changes In Peripheral and Central Immune Cell Populationssupporting

confidence: 79%

Sustained peripheral immune hyper-reactivity (SPIHR): an enduring biomarker of altered inflammatory responses in adult rats after perinatal brain injury

Kitase

Chin

Ramachandra

et al. 2021

J Neuroinflammation

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“…Functionally, MEG3 inhibits Foxp3 expression and increases RORγt expression, thus inducing imbalance between regulatory T cells and Th17 cells 12 . The imbalance between these subsets of T cells might participate in the pathogenesis of GBS or CIDP as previous studies have shown the therapeutic effects of regulatory T cells in animal models of GBS 31 .…”

Section: Discussionmentioning

confidence: 92%

Dysregulation of lncRNAs in autoimmune neuropathies

Gholipour

Taheri

Habibabadi

et al. 2021

Sci Rep

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Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Guillain-Barré syndrome (GBS) are inflammatory neuropathies with different clinical courses but similar underlying mechanisms. Long non-coding RNAs (lncRNAs) might affect pathogenesis of these conditions. In the current project, we have selected HULC, PVT1, MEG3, SPRY4-IT1, LINC-ROR and DSCAM-AS1 lncRNAs to appraise their transcript levels in the circulation of CIDP and GBS cases versus controls. Expression of HULC was higher in CIDP patients compared with healthy persons (Ratio of mean expression (RME) = 7.62, SE = 0.72, P < 0.001). While expression of this lncRNA was not different between female CIDP cases and female controls, its expression was higher in male CIDP cases compared with male controls (RME = 13.50, SE = 0.98, P < 0.001). Similarly, expression of HULC was higher in total GBS cases compared with healthy persons (RME = 4.57, SE = 0.65, P < 0.001) and in male cases compared with male controls (RME = 5.48, SE = 0.82, P < 0.001). Similar pattern of expression was detected between total cases and total controls. PVT1 was up-regulated in CIDP cases compared with controls (RME = 3.04, SE = 0.51, P < 0.001) and in both male and female CIDP cases compared with sex-matched controls. Similarly, PVT1 was up-regulated in GBS cases compared with controls (RME = 2.99, SE = 0.55, P vale < 0.001) and in total patients compared with total controls (RME = 3.02, SE = 0.43, P < 0.001). Expression levels of DSCAM-AS1 and SPRY4-IT1 were higher in CIDP and GBS cases compared with healthy subjects and in both sexes compared with gender-matched healthy persons. Although LINC-ROR was up-regulated in total CIDP and total GBS cases compared with controls, in sex-based comparisons, it was only up-regulated in male CIDP cases compared with male controls (RME = 3.06, P = 0.03). Finally, expression of MEG3 was up-regulated in all subgroups of patients versus controls except for male GBS controls. SPRY4-IT could differentiate CIDP cases from controls with AUC = 0.84, sensitivity = 0.63 and specificity = 0.97. AUC values of DSCAM-AS1, MEG3, HULC, PVT1 and LINC-ROR were 0.80, 0.75, 0.74, 0.73 and 0.72, respectively. In differentiation between GBS cases and controls, SPRY4-IT and DSCAM-AS1 has the AUC value of 0.8. None of lncRNAs could appropriately differentiate between CIDP and GBS cases. Combination of all lncRNAs could not significantly enhance the diagnostic power. Taken together, these lncRNAs might be involved in the development of CIDP or GBS.

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“…One study reported that the histone deacetylase inhibitor MS‐275 effectively suppressed inflammatory reactions, possibly by increasing the percentage of CD4 + Foxp3 + Treg cells in peripheral blood 28 . Moreover, transfusion of autologous CD4 + CD25 + regulatory T cells has been reported to be effective in alleviating inflammatory cell infiltration in the sciatic nerve in experimental autoimmune neuritis model rats 29 . However, the impaired numbers and functions of Treg cells as well as the possible regulatory mechanisms have not been fully elucidated in CP/CPPS.…”

Section: Discussionmentioning

confidence: 99%

“…28 Moreover, transfusion of autologous CD4 + CD25 + regulatory T cells has been reported to be effective in alleviating inflammatory cell infiltration in the sciatic nerve in experimental autoimmune neuritis model rats. 29 33,34 However, some studies have reported an increase in circulating Treg cells particularly in the early and active phases of disease. 35,36 One research found the proportion of Treg cells was increased in the prostatitis rodent model.…”

Section: Autophagy Activation Promoted the Developmental Restoratiomentioning

confidence: 99%

Activated autophagy restored the impaired frequency and function of regulatory T cells in chronic prostatitis

Liu

Zhang

et al. 2020

The Prostate

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Background: Chronic prostatitis or chronic pelvic pain syndrome (CP/CPPS) is a disease with an unclear pathogenesis. Recent studies have reported that regulatory T (Treg) cells might be involved in the development of CP/CPPS. In this study we aimed to examine the functional role of Treg cells and explore the possible regulatory mechanism of Treg cells in CP/CPPS. Methods: An experimental autoimmune prostatitis (EAP) mouse model was constructed; the numbers and functions of Treg cells in the EAP and control groups were tested. Then, cell differentiation experiments were conducted to evaluate the regulatory effect of autophagy on Treg cell differentiation. Furthermore, autologous CD4 + CD25cells and CD4 + CD25 + cells from the two groups were magnetically sorted and cocultured to observe differences in cellular inhibitory functions. Finally, in an in vivo experiment, rapamycin was intraperitoneally injected into EAP mice for 4 weeks to observe the therapeutic effects. Results: We found that the number and function of Treg cells in the EAP group were diminished compared to those in the control group. Meanwhile, the tolerance of pain in EAP mice had also decreased. Moreover, after using the autophagy activator rapamycin, the expression of the inflammatory cytokines interleukin-1β was decreased and the pain symptoms were alleviated. A mechanistic study found that autophagy activation promoted the differentiation of Treg and increased the suppressive functions of Treg cells, along with the elevated expression of GATA-3 and cytotoxic T lymphocyte antigen 4 (CTLA-4). Furthermore, in vivo administration of the autophagy activator rapamycin had similar effects on recovering the frequency and function of Treg cells as well as the expression of GATA-3 and CTLA-4. Conclusion: The impaired frequency and function of Treg cells may contribute to the progression of CP/CPPS, and autophagy is a protective mechanism that promotes the differentiation of Treg cells and restores the suppressive functions of Treg cells. Autophagy may be a novel therapeutic option for patients with CP/CPPS.

show abstract

Therapeutic Effect of CD4+CD25+ Regulatory T Cells Amplified In Vitro on Experimental Autoimmune Neuritis in Rats

Cited by 14 publications

References 20 publications

Sustained peripheral immune hyper-reactivity (SPIHR): an enduring biomarker of altered inflammatory responses in adult rats after perinatal brain injury

Sustained peripheral immune hyper-reactivity (SPIHR): an enduring biomarker of altered inflammatory responses in adult rats after perinatal brain injury

Dysregulation of lncRNAs in autoimmune neuropathies

Activated autophagy restored the impaired frequency and function of regulatory T cells in chronic prostatitis

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