Local level of TGF-β1 determines the effectiveness of dexamethasone through regulating the balance of Treg/Th17 cells in TNBS-induced mouse colitis

Peng, You; Chen, Ning; Su, Lin; Peng, Tao; Chen, Guodong; Liu, Yulan

doi:10.3892/etm.2018.5852

Cited by 10 publications

(8 citation statements)

References 32 publications

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“…One such factor is TGF-β, which participates in induction of Th17 and Treg cells. This differential role seems to be tissue-dependent, and TGF-β expression seems to be level-dependent [20]. Measurement of Th17-related genes in local lesions could be of immense interest for identification of new biomarkers in autoimmune diseases.…”

Section: Discussionmentioning

confidence: 99%

Differential Expression of SMAD Genes and S1PR1 on Circulating CD4+ T Cells in Multiple Sclerosis and Crohn’s Disease

Abarca-Zabalía

García

Ros

et al. 2020

IJMS

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The Th17 immune response plays a key role in autoimmune diseases such as multiple sclerosis (MS) and inflammatory bowel disease (IBD). Expression of Th17-related genes in inflamed tissues has been reported in autoimmune diseases. However, values are frequently obtained using invasive methods. We aimed to identify biomarkers of MS in an accessible sample, such as blood, by quantifying the relative expression of 91 Th17-related genes in CD4+ T lymphocytes from patients with MS during a relapse or during a remitting phase. We also compared our findings with those of healthy controls. After confirmation in a validation cohort, expression of SMAD7 and S1PR1 mRNAs was decreased in remitting disease (–2.3-fold and –1.3-fold, respectively) and relapsing disease (–2.2-fold and –1.3-fold, respectively). No differential expression was observed for other SMAD7-related genes, namely, SMAD2, SMAD3, and SMAD4. Under-regulation of SMAD7 and S1PR1 was also observed in another autoimmune disease, Crohn’s disease (CD) (−4.6-fold, -1.6-fold, respectively), suggesting the presence of common markers for autoimmune diseases. In addition, expression of TNF, SMAD2, SMAD3, and SMAD4 were also decreased in CD (–2.2-fold, –1.4-fold, –1.6-fold, and –1.6-fold, respectively). Our study suggests that expression of SMAD7 and S1PR1 mRNA in blood samples are markers for MS and CD, and TNF, SMAD2, SMAD3, and SMAD4 for CD. These genes could prove useful as markers of autoimmune diseases, thus obviating the need for invasive methods.

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Section: Discussionmentioning

confidence: 99%

Differential Expression of SMAD Genes and S1PR1 on Circulating CD4+ T Cells in Multiple Sclerosis and Crohn’s Disease

Abarca-Zabalía

García

Ros

et al. 2020

IJMS

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“…Interestingly, rLZ‐8 failed to do so. Thus, DEX likely ameliorates allergic pulmonary inflammation by down‐regulating Th2 response in asthma 26,27 while rLZ‐8 does not.…”

Section: Discussionmentioning

confidence: 99%

A recombinant protein rLZ-8, originally extracted from Ganoderma lucidum, ameliorates OVA-induced lung inflammation by regulating Th17/Treg balance

Liu

Qiu

Wang

et al. 2020

Journal of Leukocyte Biology

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Asthma is one of the most common chronic and inflammatory respiratory diseases, which is estimated to affect 1-10% of the population in different regions across the world. Previous studies have shown that recombinant Ling-Zhi 8 (rLZ-8), an immunoregulatory protein originally extracted from Ganoderma lucidum, plays multiple roles in regulating murine immune cells, including T cells. Here, we examined whether rLZ-8 would ameliorate pulmonary inflammation in a model of asthma-like mice. We found that rLZ-8 significantly inhibited the lung inflammation and reduced infiltration of inflammatory cells, including dendritic cells and eosinophils, in OVAinduced asthmatic mice. It also deceased IL-17A level but increased IL-10 level in bronchoalveolar lavage fluid (BALF) while reducing ROR t mRNA expression and enhancing Foxp3 mRNA level in the lung tissue. Flow cytometry studies demonstrated that rLZ-8 remarkably down-regulated Th17 cells but upregulated Foxp3 + regulatory T (Treg) cells, rather than influencing Th1 versus Th2 cells. Experiments in vitro also showed that rLZ-8 suppressed murine CD3 + T cell proliferation and reduced the frequency of Th17 cells while promoting the differentiation of CD4 + Foxp3 + Tregs. Moreover, rIL-8 similarly altered human Th17/Treg generation or their balance in vitro. Finally, we found that rLZ-8 suppressed signaling pathways of both STAT3 and NF-B (P100/P52) in murine lung tissue as well as cultured T cells. Thus, we have demonstrated that rLZ-8 attenuates pulmonary inflammation through regulating the balance of Th17/Treg cells in OVA-induced asthmatic mice and that rLZ-8 may be a potential therapeutic agent for the treatment of asthma in clinic. K E Y W O R D S herbal ingredient, pulmonary inflammation, Th cell, treg 1 INTRODUCTION Asthma, a chronic inflammatory airway disease associated with reversible airflow obstruction and persistent airway hyperresponsiveness, is a major public health problem that affects 300 million people worldwide. Although asthma is relatively well controlled by the most Abbreviations: BALF, bronchoalveolar lavage fluid; DC, dendritic cell; DEX, dexamethasone; rLZ-8, recombinant Ling-Zhi protein-8; Treg, regulatory T cell. effective first-line treatment, including inhaled corticosteroids, an estimated 40% of asthmatics fail to respond to corticosteroid and show no improvement in airway function. 1 In addition, various side effects resulting from the long-term use of these agents necessitate alternative therapeutic options. Allergen-specific CD4 + T cells have been shown to play a key role in the development of asthma. 2 In patients with the mild to moderate asthma, the classic mode of onset is that specific IgE Abs of B cells induced by CD4 + Th2 cells mediate immune responses and

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“…Low amounts of TGF-β1 directly delivered into the colon reduced colonic inflammation and restored Treg cell numbers. Dex supported the differentiation of Treg cells in the presence of TGF-β1 and alleviated clinical symptoms, indicating that the activity of GCs in the treatment of colitis may depend on an interaction of the GR with components of TGF-β1 signaling [ 92 ].…”

Section: Gcs In the Pathogenesis And Treatment Of Inflammatory Diseasesmentioning

confidence: 99%

The Role of Glucocorticoids in Inflammatory Diseases

Reichardt

Amouret

Muzzi

et al. 2021

Cells

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For more than 70 years, glucocorticoids (GCs) have been a powerful and affordable treatment option for inflammatory diseases. However, their benefits do not come without a cost, since GCs also cause side effects. Therefore, strong efforts are being made to improve their therapeutic index. In this review, we illustrate the mechanisms and target cells of GCs in the pathogenesis and treatment of some of the most frequent inflammatory disorders affecting the central nervous system, the gastrointestinal tract, the lung, and the joints, as well as graft-versus-host disease, which often develops after hematopoietic stem cell transplantation. In addition, an overview is provided of novel approaches aimed at improving GC therapy based on chemical modifications or GC delivery using nanoformulations. GCs remain a topic of highly active scientific research despite being one of the oldest class of drugs in medical use.

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Local level of TGF-β1 determines the effectiveness of dexamethasone through regulating the balance of Treg/Th17 cells in TNBS-induced mouse colitis

Cited by 10 publications

References 32 publications

Differential Expression of SMAD Genes and S1PR1 on Circulating CD4+ T Cells in Multiple Sclerosis and Crohn’s Disease

Differential Expression of SMAD Genes and S1PR1 on Circulating CD4+ T Cells in Multiple Sclerosis and Crohn’s Disease

A recombinant protein rLZ-8, originally extracted from Ganoderma lucidum, ameliorates OVA-induced lung inflammation by regulating Th17/Treg balance

The Role of Glucocorticoids in Inflammatory Diseases

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