IL-4 enhances IL-10 production in Th1 cells: implications for Th1 and Th2 regulation

Mitchell, Ruth; Hassan, Masriana; Burton, Bronwen R; Britton, Graham J.; Hill, E.; Verhagen, Johan; Wraith, David C.

doi:10.1038/s41598-017-11803-y

Cited by 78 publications

(58 citation statements)

References 54 publications

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“…Lactobacillus casei and L. rhamnosus induce IL-10 production in allergic patients by regulating the composition of intestinal microbial flora ( D’Inca et al, 2011 ). IL-10 production in Th2 cells was suppressed by IL-4 and GATA3 ( Zhu et al, 2004 ; Mitchell et al, 2017 ). Given that Duolac ATP decreased IL-4 and GATA3 expression while increasing STAT4 levels, it is unlikely that IL-10 was secreted in Th2 cells.…”

Section: Discussionmentioning

confidence: 99%

A Probiotic Mixture Regulates T Cell Balance and Reduces Atopic Dermatitis Symptoms in Mice

et al. 2018

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Atopic dermatitis (AD) is a chronic inflammatory skin disorder with a complex etiology involving the immune response. Recent studies have demonstrated the role of certain probiotics in the treatment and prevention of AD. However, the mechanism by which these probiotics regulate the immune system remains unclear. In this study, we examined the immunomodulatory capacity of Duolac ATP, a mixed formulation of probiotics, both in vitro and in vivo. Results showed that the expression of programmed death-ligand 1(PD-L1) was significantly upregulated on bone marrow-derived dendritic cells (BMDCs) treated with Duolac ATP. Furthermore, the anti-inflammatory cytokines IL-10 and TGF-beta were both upregulated when BMDCs were treated with Duolac ATP. The percentage of proliferated regulatory T cells (Tregs) was enhanced when CD4+ T cells were co-cultured with Duolac ATP-treated BMDCs on plates coated with anti-CD3/CD28 antibodies. Intriguingly, IL-10 secretion from CD4+ T cells was also observed. The AD symptoms, histologic scores, and serum IgE levels in AD mice were significantly decreased after oral treatment with Duolac ATP. Moreover, the Th1-mediated response in AD-induced mice treated with oral Duolac ATP showed upregulation of IL-2 and IFN-gamma as well as of downstream signaling molecules T-bet, STAT-1, and STAT-4. Conversely, Duolac ATP suppressed Th2 and Th17 responses in AD-like mice, as evidenced by the downregulation of GATA-3, C-maf, IL-4, IL-5, and IL-17. Additionally, Duolac ATP increased the number of Tregs found at Peyer’s patches (PP) in treated AD mice. These results suggest that Duolac ATP modulates DCs to initiate both Th1 and Treg responses in AD mice. Thus, Duolac ATP represents a potential preventative agent against AD and could serve as an effective immunomodulator in AD patients.

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Section: Discussionmentioning

confidence: 99%

A Probiotic Mixture Regulates T Cell Balance and Reduces Atopic Dermatitis Symptoms in Mice

et al. 2018

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“…Among the e-cigs users, a significant association between LLM and lung inflammatory cytokines IL-4 and IL-10 was found, but not other cytokines associated with smoking [14] . Unlike the other cytokines that were tested, IL-4 and IL-10 play a role as an immune suppressor and are required to avoid inflammation and maintain tissue homeostasis [ 18 , 19 ]. IL-4 promotes macrophage activation into the M2 phenotype, and M2 macrophages produce IL-10 [20] .…”

Section: Discussionmentioning

confidence: 99%

Lipid laden macrophages and electronic cigarettes in healthy adults

et al. 2020

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Background An outbreak of E-cigarette or Vaping Product Use-Associated Lung Injury (EVALI) with significant morbidity and mortality was reported in 2019. While most patients with EVALI report vaping tetrahydrocannabinol (THC) oils contaminated with vitamin E acetate, a subset report only vaping with nicotine-containing electronic cigarettes (e-cigs). Whether or not e-cigs cause EVALI, the outbreak highlights the need for identifying long term health effects of e-cigs. EVALI pathology includes alveolar damage, pneumonitis and/or organizing pneumonia, often with lipid-laden macrophages (LLM). We assessed LLM in the lungs of healthy smokers, e-cig users, and never-smokers as a potential marker of e-cig toxicity and EVALI. Methods A cross-sectional study using bronchoscopy was conducted in healthy smokers, e-cig users, and never-smokers ( n = 64). LLM, inflammatory cell counts, and cytokines were determined in bronchial alveolar fluids (BAL). E-cig users included both never-smokers and former light smokers. Findings High LLM was found in the lungs of almost all smokers and half of the e-cig users, but not those of never-smokers. LLM were not related to THC exposure or smoking history. LLM were significantly associated with inflammatory cytokines IL-4 and IL-10 in e-cig users, but not smoking-related cytokines. Interpretation This is the first report of lung LLM comparing apparently healthy smokers, e-cig users, and never-smokers. LLM are not a specific marker for EVALI given the frequent positivity in smokers; whether LLMs are a marker of lung inflammation in some e-cig users requires further study. Funding The National Cancer Institute, the National Heart, Lung, and Blood Institute, the Food and Drug Administration Center for Tobacco Products, the National Center For Advancing Translational Sciences, and Pelotonia Intramural Research Funds

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“…2 cells mainly secrete cytokines such as IL-4, IL-5, IL-10, and IL-13, which are involved in humoral immunity. It is generally believed that 2 cytokines can inhibit the differentiation of CD4 + T cells into 1 cells and weaken the immune response to antitumor effect, thus promoting the development of tumors [34,35].…”

Section: Discussionmentioning

confidence: 99%

Yupingfeng Granule Improves Th2-Biased Immune State in Microenvironment of Hepatocellular Carcinoma through TSLP-DC-OX40L Pathway

Yao

Yuan

Song

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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The tumor immunological microenvironment in hepatocellular carcinoma (HCC) is the T-helper (Th) 2 dominant inhibition state. Improving the immunosuppressive tumor microenvironment represents an important strategy for HCC treatment. TSLP-OX40L pathway is a target to improve Th2 immunosuppression. Yupingfeng granule (YPF) is clinically used to effectively improve the immune status of HCC. In this study, YPF increased the percentage of mature dendritic cells (DCs) and decreased levels of TSLP, TSLPR, and OX40L in tumor and adjacent tissues of the orthotopic-HCC mice model. This occurs together with the decreased levels of Th2 cytokines and increased levels of Th1 cytokines and Th1/Th2 ratio. In vitro experiment showed that YPF not only increased the percentage of mature DCs and stimulated IL-12 secretion in DCs but also reduced the positive rate of OX40L expression, decreased the proportion of CD4+ IL-13+ T cells, increased levels of Th1 cytokines, and decreased levels of Th2 cytokines from TSLP-treated DCs. In summary, these findings demonstrated that YPF promoted the maturation of DCs, decreased OX40L in TSLP-induced DCs, and improved the immunosuppressive state of Th2 in HCC microenvironment. Our results suggest that the mechanism underlying the improving effect of YPF on the immunosuppression is related to the DC-mediated TSLP-OX40L pathway.

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IL-4 enhances IL-10 production in Th1 cells: implications for Th1 and Th2 regulation

Cited by 78 publications

References 54 publications

A Probiotic Mixture Regulates T Cell Balance and Reduces Atopic Dermatitis Symptoms in Mice

A Probiotic Mixture Regulates T Cell Balance and Reduces Atopic Dermatitis Symptoms in Mice

Lipid laden macrophages and electronic cigarettes in healthy adults

Yupingfeng Granule Improves Th2-Biased Immune State in Microenvironment of Hepatocellular Carcinoma through TSLP-DC-OX40L Pathway

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