Differentiation of Pathogenic Th17 Cells Is Negatively Regulated by Let-7 MicroRNAs in a Mouse Model of Multiple Sclerosis

Angelou, Constance C; Wells, Alexandria; Vijayaraghavan, Jyothi; Dougan, Carey E.; Lawlor, Rebecca; Iverson, Elizabeth; Lazarevic, Vanja; Kimura, Motoko; Peyton, Shelly R.; Minter, Lisa M.; Osborne, Barbara A.; Pobezinskaya, E. L.; Pobezinsky, Leonid A

doi:10.3389/fimmu.2019.03125

Cited by 42 publications

(50 citation statements)

References 68 publications

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“…We then computed the correlation between the CSF levels of each inflammatory protein and let-7b-5p. Importantly, as reported in Table 2 and Figure 3A', we observed that let-7b-5p positively correlated with all members of the Cluster 1, and negatively correlated with most inflammation-related factors belonging to the Cluster 2, including also experimentally-validated targets or pathways of let-7 family, like IL6 [65][66][67][68], IL10 [15,69] and IL17 pathway [12]. To further investigate the involvement of let-7b-5p in MS pathology, we compared the miRNA levels in the CSF between control subjects and the main cohort of patients with MS. We observed a highly variable expression among the patients respect to control subjects (Ctr: n = 20; MS: n = 166; Mann-Whitney test, p > 0.05) ( Figure 4A).…”

Section: Let-7b-5p Is a Putative Anti-inflammatory Regulator Of The Csupporting

confidence: 72%

The microRNA let-7b-5p Is Negatively Associated with Inflammation and Disease Severity in Multiple Sclerosis

Mandolesi

Rizzo

Balletta

et al. 2021

Cells

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The identification of microRNAs in biological fluids for diagnosis and prognosis is receiving great attention in the field of multiple sclerosis (MS) research but it is still in its infancy. In the present study, we observed in a large sample of MS patients that let-7b-5p levels in the cerebrospinal fluid (CSF) were highly correlated with a number of microRNAs implicated in MS, as well as with a variety of inflammation-related protein factors, showing specific expression patterns coherent with let-7b-5p-mediated regulation. Additionally, we found that the CSF let-7b-5p levels were significantly reduced in patients with the progressive MS compared to patients with relapsing-remitting MS and were negatively correlated with characteristic hallmark processes of the two phases of the disease. Indeed, in the non-progressive phase, let-7b-5p inversely associated with both central and peripheral inflammation; whereas, in progressive MS, the CSF levels of let-7b-5p negatively correlated with clinical disability at disease onset and after a follow-up period. Overall, our results uncovered, by the means of a multidisciplinary approach and multiple statistical analyses, a new possible pleiotropic action of let-7b-5p in MS, with potential utility as a biomarker of MS course.

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Section: Let-7b-5p Is a Putative Anti-inflammatory Regulator Of The Csupporting

confidence: 72%

The microRNA let-7b-5p Is Negatively Associated with Inflammation and Disease Severity in Multiple Sclerosis

Mandolesi

Rizzo

Balletta

et al. 2021

Cells

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“…MS is a chronic inflammatory disease of the central nervous system (CNS). Th17 pathogenicity in MS has been correlated with the dysregulation of the expression of microRNAs (miRNAs), and specific miRNAs promote the pathogenic phenotype [ 138 ]. In MS, autoreactive Th17 cells, generated by IL-23 and IL-1β, migrate to the CNS and cross the blood–brain barrier.…”

Section: T Helper 17 Cells (Th17)mentioning

confidence: 99%

“…In MS, autoreactive Th17 cells, generated by IL-23 and IL-1β, migrate to the CNS and cross the blood–brain barrier. In encephalitogenic Th17 cells, the Bhlhe40 transcription factor, which is induced by IL-1β signalling, positively regulates the secretion of GM-CSF and consequently, GM-CSF-stimulated glial and dendritic cells reinforce the differentiation and maintenance of pathogenic Th17 cells, by secreting IL-6 and IL-23 [ 138 ].…”

Section: T Helper 17 Cells (Th17)mentioning

confidence: 99%

The Many Faces of CD4+ T Cells: Immunological and Structural Characteristics

Chatzileontiadou

Sloane

Nguyen

et al. 2020

IJMS

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As a major arm of the cellular immune response, CD4+ T cells are important in the control and clearance of infections. Primarily described as helpers, CD4+ T cells play an integral role in the development and activation of B cells and CD8+ T cells. CD4+ T cells are incredibly heterogeneous, and can be divided into six main lineages based on distinct profiles, namely T helper 1, 2, 17 and 22 (Th1, Th2, Th17, Th22), regulatory T cells (Treg) and T follicular helper cells (Tfh). Recent advances in structural biology have allowed for a detailed characterisation of the molecular mechanisms that drive CD4+ T cell recognition. In this review, we discuss the defining features of the main human CD4+ T cell lineages and their role in immunity, as well as their structural characteristics underlying their detection of pathogens.

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“…Therefore, the future functional characterization of rEg.P29 may further the understanding of the molecular mechanism associated with rEg.P29. MicroRNAs are critical for a broad range of biological processes, including T cell homeostasis and activation [16,18,30]. Over recent years, accumulating data have also shown that miRNAs are important for modulating CD4 + T cell differentiation and plasticity [31].…”

Section: Discussionmentioning

confidence: 99%

MiR-374b-5p Regulates T Cell Differentiation and Is Associated with rEg.P29 Immunity

Zhu

et al. 2020

BioMed Research International

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Cystic echinococcosis (CE) is a zoonotic disease caused by Echinococcus granulosus (Eg) infection. Our previous study confirmed that recombinant Eg.P29 (rEg.P29) could protect against echinococcus granulosus secondary infection in sheep and mice. The aim of the study was to investigate the association between immunoprotection of rEg.P29 vaccine and mmu-miR-374b-5p (miR-374b-5p) and study the immunity influence of miR-374b-5p on CD4+ T cells in mice spleen. MiR-374b-5p level was significantly increased after the second-week and the fourth week of vaccination with rEg.P29. Overexpression of miR-374b-5p increased IFN-γ, IL-2, IL-17A mRNA levels and decreased IL-10 mRNA levels in CD4+ T cells. Moreover, the inhibition of miR-374b-5p decreased IFN-γ and IL-17A and increased IL-10 mRNA levels in CD4+ T cells; this was further confirmed by the flow cytometry. The vaccination of rEg.P29 enhanced miR-374b-5p expression that was associated with a higher Th1 and Th17 immune response, a lower IL-10 mRNA production with miR-374b-5p overexpression, a lower Th1 immune response, and a higher IL-10 mRNA levels with miR-374b-5p inhibitions. To sum up, these data suggest that miR-374b-5p may participate in rEg.P29 immunity by regulating Th1 and Th17 differentiation.

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Differentiation of Pathogenic Th17 Cells Is Negatively Regulated by Let-7 MicroRNAs in a Mouse Model of Multiple Sclerosis

Cited by 42 publications

References 68 publications

The microRNA let-7b-5p Is Negatively Associated with Inflammation and Disease Severity in Multiple Sclerosis

The microRNA let-7b-5p Is Negatively Associated with Inflammation and Disease Severity in Multiple Sclerosis

The Many Faces of CD4+ T Cells: Immunological and Structural Characteristics

MiR-374b-5p Regulates T Cell Differentiation and Is Associated with rEg.P29 Immunity

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