The Heat Shock Protein HSP70 Promotes Th17 Genes’ Expression via Specific Regulation of microRNA

Ćwiklińska, Hanna; Cichalewska-Studzinska, Maria; Selmaj, Krzysztof; Mycko, Marcin P.

doi:10.3390/ijms21082823

Cited by 11 publications

(9 citation statements)

References 56 publications

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“…The activity of heat shock protein 70 in Th17 promotion depends on the regulation of a set of speci c miRNA expression. Selective inhibition of these microRNAs or directly blocking the function of heat shock protein 70 will downregulate the expression of Th17 gene [40].…”

Section: Discussionmentioning

confidence: 99%

The Abnormal Expression of HSP70 Is Related to Treg / Th17 Imbalance in PCOS Patients

Yang¹,

Xia²,

Yang³

et al. 2021

Preprint

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Background: Polycystic ovary syndrome (PCOS) is a disease with chronic nonspecific low-grade inflammation. The imbalance of immune cells exists in PCOS. Several studies have found that heat shock protein 70 (HSP70) may be involved in the immunological pathogenesis of PCOS, but the relationship between HSP70 and Regulatory T cell (Treg)/ T helper cell 17(Th17) ratio remains unclear. This study aims to explore the correlation between HSP70 and Treg/Th17 ratio, and to find out the role of HSP70 in the immunological etiology of PCOS.Results: There was no significant difference in age and body mass index (BMI) between two groups. The concentrations of basal estradiol (E2), basal follicle stimulating hormone (FSH) didn’t show significant difference between two groups. The concentrations of basal luteinizing hormone (LH) (P < 0.05), testosterone (T) (P < 0.01), glucose (P < 0.001) and insulin (P < 0.001) in PCOS patients were significantly higher than those in control group. The expressions of HSP70 were significantly higher in serum in the PCOS group (P < 0.001). The percentage of Treg cells was significantly lower (P < 0.05), while the percentage of the Th17 cells of the PCOS group was significantly higher than that of the control group (P < 0.05). The ratio of Treg/Th17 in PCOS group was significantly lower (P < 0.001). The concentrations of Interleukin (IL)-6, IL-17 and IL-23 were significantly higher, while the levels of IL-10 and Transforming growth factor-β (TGF-β) were significantly lower in PCOS group (P < 0.001). Spearman rank correlation analysis showed strong negative correlation of serum HSP70 levels with Treg/Th17 ratio, IL-10 and TGF-β levels. In contrast, HSP70 levels were significantly positively correlated with IL-6, IL-17, IL-23, LH, T, insulin, and glucose levels.Conclusion: The abnormal expression of HSP70 is correlated with Treg/Th17 imbalance and corresponding cytokines, which indicates that HSP70 may play an important role in PCOS immunologic pathogenesis.

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Section: Discussionmentioning

confidence: 99%

The Abnormal Expression of HSP70 Is Related to Treg / Th17 Imbalance in PCOS Patients

Yang¹,

Xia²,

Yang³

et al. 2021

Preprint

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“…Importantly, HSP90 are required for stable binding of Argonaute to Dicer, enzyme responsible for processing of small interfering RNAs and miRNAs in the cytoplasm for their further loading on RNA-induced silencing complex (RISC) [279] , [280] , [281] . HSP70 also showed to be associated with Ago2 following T-cell receptor (TCR) activation for the regulation of T-helper 17 (Th17) cells via miRNA expression in EL-4 murine lymphoma cells [282] .…”

Section: Hsps and Micrornasmentioning

confidence: 99%

Extracellular heat shock proteins and cancer: New perspectives

Albakova

Siam

Sacitharan

et al. 2021

Translational Oncology

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Highlights High expression of extracellular heat shock proteins (HSPs) indicates highly aggressive tumors. HSP profiling of extracellular vesicles (EVs) derived from various biological fluids and released by immune cells may open new perspectives for an identification of diagnostic, prognostic and predictive biomarkers of cancer. Identification of specific microRNAs targeting HSPs in EVs may be a promising strategy for the discovery of novel biomarkers of cancer.

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“…Currently more than 200 other genetic variants are known to confer the risk to develop the disease, and their role is probably mediated by immune pathway genes [8,9]. In addition to a genetic susceptibility, a number of epigenetic mechanisms operate in MS [10][11][12]. The fact that most of the genetic predisposition for MS is conferred by the DR15 haplotype supports the role of T helper cells (Th, CD4+ T cells), since CD4+ T cells recognise antigen in the context of HLA class II molecules [7,13].…”

Section: Autoimmune Mechanisms In Msmentioning

confidence: 99%

B cell targeting therapies in MS patients during the SARS-CoV-2 pandemic — when immunosuppression meets infection?

Mycko

2020

Neurol Neurochir Pol.

Self Cite

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Introduction. Research into the mechanisms of autoimmune demyelination have highlighted B cells in this process. Therapies targeting this population were a recent addition to the multiple sclerosis (MS) drugs portfolio. The SARS-CoV-2 pandemic and the risk of severe COVID-19 have challenged the safety of B cell depletion in MS patients. State of the art. Selective depletion of B cells by monoclonal antibodies as monotherapy in MS has been shown to profoundly suppress disease activity among relapsing-remitting MS patients. Furthermore ocrelizumab, a humanised anti-CD20 monoclonal antibody, was the first licensed therapy in primary progressive MS. Based on the concept of the role of B cells in MS, many therapeutic approaches are emerging as novel ways to treat autoimmune demyelination. However, during the SARS-CoV-2 pandemic, a conservative approach toward limiting immune suppression in MS patients has been proposed. Clinical implications. Emerging evidence does not support the notion of increased susceptibility among MS patients to the SARS-CoV-2 infection, or any predisposition toward greater severity of COVID-19. This also does not appear to be the case for MS patients undergoing B cell depletion therapies. Thus, any decision to withhold immune suppression in MS patients during the SARS-CoV-2 pandemic is probably incorrect. MS therapeutic decision-making should focus on the danger of poorly controlled autoimmune demyelination rather than perceived risks from COVID-19. Future directions. The current pandemic highlights the need to develop more selective and safer methods of immunomodulation in MS. B cells represent several functionally different populations. Further research into the different role of these cells during autoimmune demyelination should yield better, safer strategies to control the encephalitogenic process.

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The Heat Shock Protein HSP70 Promotes Th17 Genes’ Expression via Specific Regulation of microRNA

Cited by 11 publications

References 56 publications

The Abnormal Expression of HSP70 Is Related to Treg / Th17 Imbalance in PCOS Patients

The Abnormal Expression of HSP70 Is Related to Treg / Th17 Imbalance in PCOS Patients

Extracellular heat shock proteins and cancer: New perspectives

B cell targeting therapies in MS patients during the SARS-CoV-2 pandemic — when immunosuppression meets infection?

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