Increased CD4+CD45RA-FoxP3lowcells alter the balance between Treg and Th17 cells in colitis mice

Ma, Yahui; Zhang, Jie; Xue, Chen; Xie, You-Fu; Pang, Yanbo; Liu, Xinjuan

doi:10.3748/wjg.v22.i42.9356

Cited by 13 publications

(7 citation statements)

References 53 publications

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“…Experimental model of IBD showed an increase in Tregs percentage in the inflamed ileum with a reduced immunosuppressive function and IL-10 production. The dysregulated expression between Th17 cells and Tregs was also observed in UC animal model with downregulated mRNA expression of Foxp3 and IL-10 levels in Trges [149]. In UC patients, a significant increase of IL-17 and Th17 cells and a simultaneous decrease of TGF-β and Trges in serum as compared to healthy control was seen [150].…”

Section: Therapeutic Role Of Tregs In Ibdmentioning

confidence: 80%

Translating Treg Therapy for Inflammatory Bowel Disease in Humanized Mice

Negi

Saini

Tandel

et al. 2021

Cells

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Crohn’s disease and ulcerative colitis, two major forms of inflammatory bowel disease (IBD) in humans, afflicted in genetically predisposed individuals due to dysregulated immune response directed against constituents of gut flora. The defective immune responses mounted against the regulatory mechanisms amplify and maintain the IBD-induced mucosal inflammation. Therefore, restoring the balance between inflammatory and anti-inflammatory immunepathways in the gut may contribute to halting the IBD-associated tissue-damaging immune response. Phenotypic and functional characterization of various immune-suppressive T cells (regulatory T cells; Tregs) over the last decade has been used to optimize the procedures for in vitro expansion of these cells for developing therapeutic interventional strategies. In this paper, we review the mechanisms of action and functional importance of Tregs during the pathogenesis of IBD and modulating the disease induced inflammation as well as role of mouse models including humanized mice repopulated with the human immune system (HIS) to study the IBD. “Humanized” mouse models provide new tools to analyze human Treg ontogeny, immunobiology, and therapy and the role of Tregs in developing interventional strategies against IBD. Overall, humanized mouse models replicate the human conditions and prove a viable tool to study molecular functions of human Tregs to harness their therapeutic potential.

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Section: Therapeutic Role Of Tregs In Ibdmentioning

confidence: 80%

Translating Treg Therapy for Inflammatory Bowel Disease in Humanized Mice

Negi

Saini

Tandel

et al. 2021

Cells

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“… 52 , 53 It is also known that the level of Th17 cell was increased in PBMCs, and the expression of IL-17A messenger RNA were increased in the PBMCs, mesenteric lymph node, and lamina propria of colon of dextran sulfate sodium colitis mice. 54 Above all, type 17 immunity is one of the important systemic changes in UC.…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Population-Specific Cell Subsets in Chinese Ulcerative Colitis Patients Using Single-Cell RNA Sequencing

Zhang

Hao

et al. 2021

Cellular and Molecular Gastroenterology and Hepatology

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Background & Aims Genome-wide association studies (GWAS) and transcriptome analyses have been performed to better understand the pathogenesis of ulcerative colitis (UC). However, current studies mainly focus on European ancestry, highlighting a great need to identify the key genes, pathways and cell types in colonic mucosal cells of adult UC patients from other ancestries. Here we aimed to identify key genes and cell types in colonic mucosal of UC. Methods We performed Single-cell RNA sequencing (scRNA-seq) analysis of 12 colon biopsies of UC patients and healthy controls from Chinese Han ancestry. Results Two novel plasma subsets were identified. Five epithelial/stromal and three immune cell subsets show significant difference in abundance between inflamed and non-inflamed samples. In general, UC risk genes show consistent expression alteration in both Immune cells of inflamed and non-inflamed tissues. As one of the exceptions, IgA defection, marking the signal of immune dysfunction, is specific to the inflamed area. Moreover, Th17 derived activation was observed in both epithelial cell lineage and immune cell lineage of UC patients as compared to controls , suggesting a systemic change of immune activities driven by Th17. The UC risk genes show enrichment in progenitors, glial cells and immune cells, and drug-target genes are differentially expressed in antigen presenting cells. Conclusions Our work identifies novel population-specific plasma cell molecular signatures of UC. The transcriptional signature of UC is shared in immune cells from both inflamed and non-inflamed tissues, whereas the transcriptional response to disease is a local effect only in inflamed epithelial/stromal cells.

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“…The flow cytometry analysis was performed as previously described with minor modifications ( Ma et al, 2016 ). Briefly, cells were incubated with CD4 and CD25, followed by fixation in fixation/permeabilization buffer.…”

Section: Methodsmentioning

confidence: 99%

Yanghe Decoction Suppresses the Experimental Autoimmune Thyroiditis in Rats by Improving NLRP3 Inflammasome and Immune Dysregulation

Chen

Liu

et al. 2021

Front. Pharmacol.

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Inflammation is an important contributor to autoimmune thyroiditis. Yanghe decoction (YH) is a traditional Chinese herbal formulation which has various anti-inflammatory effects. It has been used for the treatment of autoimmune diseases such as ankylosing spondylitis In this study we aimed to investigate the effects of YH on autoimmune thyroiditis in a rat model and elucidate the underlying mechanisms. The experimental autoimmune thyroiditis (EAT) model was established by thyroglobulin (pTG) injections and excessive iodine intake. Thyroid lesions were observed using hematoxylin and eosin (H and E) staining and serum TgAb, TPOAb, TSH, T3, and T4 levels were measured by enzyme-linked immunosorbent assay IL-35 levels were evaluated using real-time polymerase chain reaction (RT-PCR) and Th17/Treg balance in peripheral blood mononuclear cells (PBMCs) was determined by flow cytometry and RT-PCR. Changes in Wnt/β-catenin signaling were evaluated using Western blot. Immunofluorescence staining and western blot were employed to examine NLRP3 inflammasome activation in the thyroid. YH minimized thyroid follicle injury and decreased concentrations of serum TgAb, TPOAb, TSH, T3, and T4 in EAT model. The mRNA of IL-35 was increased after YH treatment. YH also increased the percentage of Treg cells, and decreased Th17 proportion as well as Th17/Treg ratio in PBMCs. Meanwhile, the mRNA levels of Th17 related cytokines (RORγt, IL-17A, IL-21, and IL-22) were suppressed and Treg related cytokines (FoxP3, TGF-β, and IL-10) were promoted in PBMCs. Additionally, the protein expressions of Wnt-1 and β-catenin were unregulated after YH treatment. NLRP3 immunostaining signal and protein levels of IL-17, p-NF-κB, NLRP3, ASC, cleaved-Caspase-1, cleaved-IL-1β, and IL-18 were downregulated in the thyroid after YH intervention. Overall, the present study demonstrated that YH alleviated autoimmune thyroiditis in rats by improving NLRP3 inflammasome and immune dysregulation.

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Increased CD4⁺CD45RA^-FoxP3^lowcells alter the balance between Treg and Th17 cells in colitis mice

Cited by 13 publications

References 53 publications

Translating Treg Therapy for Inflammatory Bowel Disease in Humanized Mice

Translating Treg Therapy for Inflammatory Bowel Disease in Humanized Mice

Identification of Novel Population-Specific Cell Subsets in Chinese Ulcerative Colitis Patients Using Single-Cell RNA Sequencing

Yanghe Decoction Suppresses the Experimental Autoimmune Thyroiditis in Rats by Improving NLRP3 Inflammasome and Immune Dysregulation

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