Cell Mol Gastroenterol Hepatol
April 2023
Background & Aims: T helper 1 (Th1) effector cells are implicated in inflammatory bowel disease. The stimulator of interferon genes (STING), an intracellular DNA sensor, has been shown to regulate infection and various cancers. However, whether and how intrinsic STING signaling in Th1 cells regulates colitis is still unknown.
View Article and Find Full Text PDFBackground: Intestinal Immunoglobulin A (IgA) is crucial in maintaining host-microbiota mutualism and gut homeostasis. It has been shown that many species of gut bacteria produce cyclic dinucleotides, along with an abundance of microbiota-derived DNA present within the intestinal lumen, which triggers the tonic activation of the cytosolic cGAS-STING pathway. However, the role of STING in intestinal IgA remains poorly understood.
View Article and Find Full Text PDFBackground & Aims: Intestinal fibrosis is a significant complication of Crohn's disease (CD). Gut microbiota reactive Th17 cells are crucial in the pathogenesis of CD; however, how Th17 cells induce intestinal fibrosis is still not completely understood.
Methods: In this study, T-cell transfer model with wild-type (WT) and Areg Th17 cells and dextran sulfate sodium (DSS)-induced chronic colitis model in WT and Areg mice were used.
Glucose, the critical energy source in the human body, is considered a potential risk factor in various autoimmune diseases when consumed in high amounts. However, the roles of glucose at moderate doses in the regulation of autoimmune inflammatory diseases and CD4 T cell responses are controversial. Here, we show that while glucose at a high concentration (20% w/v) promotes intestinal inflammation, it suppresses colitis at a moderate dose (6% w/v), which increases the proportion of intestinal regulatory T (Treg) cells but does not affect effector CD4 T cells.
View Article and Find Full Text PDFBackground & Aims: G protein-coupled receptor (GPR) 120 has been implicated in regulating metabolic syndromes with anti-inflammatory function. However, the role of GPR120 in intestinal inflammation is unknown. Here, we investigated whether and how GPR120 regulates CD4 T cell function to inhibit colitis development.
View Article and Find Full Text PDFAn uncontrolled CD4 T cell response is a critical hallmark of autoimmune diseases. IL-10, which can be produced by both effector and regulatory CD4 T cells, plays an essential role in the inhibition of autoimmunity. MicroRNAs are key molecules involved in regulating immune responses.
View Article and Find Full Text PDFCell Mol Gastroenterol Hepatol
March 2022
Background And Aims: Gut bacteria-derived short-chain fatty acids (SCFAs) play crucial roles in the maintenance of intestinal homeostasis. However, how SCFAs regulate epithelial turnover and tissue repair remain incompletely understood. In this study, we investigated how the SCFA propionate regulates cell migration to promote epithelial renewal and repair.
View Article and Find Full Text PDFStimulator of interferon genes (STING) has been shown to play a critical role in orchestrating immune responses to various pathogens through sensing cyclic dinucleotides. However, how STING regulates intestinal homeostasis is still not completely understood. In this study, we found that STING mice were more susceptible to enteric infection with Citrobacter rodentium compared to wild-type (WT) mice evidenced by more severe intestinal inflammation and impaired bacterial clearance.
View Article and Find Full Text PDFInnate lymphoid cells (ILCs) and CD4 T cells produce IL-22, which is critical for intestinal immunity. The microbiota is central to IL-22 production in the intestines; however, the factors that regulate IL-22 production by CD4 T cells and ILCs are not clear. Here, we show that microbiota-derived short-chain fatty acids (SCFAs) promote IL-22 production by CD4 T cells and ILCs through G-protein receptor 41 (GPR41) and inhibiting histone deacetylase (HDAC).
View Article and Find Full Text PDFThe role of IL-21, produced mainly by Th17 cells and T follicular helper cells, has been intensively investigated in B cell differentiation and Ab class switch. However, how IL-21 regulates memory IgA B cell development and memory IgA responses in the intestines is still not completely understood. In this study, we found the total IgA B cells as well as CD38CD138IgA memory B cells were significantly increased in intestinal lamina propria (LP) of TCRβxδ mice after transfer of microbiota Ag-specific Th17 cells but not Th1 cells.
View Article and Find Full Text PDFBackground: Shigella spp., facultative anaerobic bacilli of the family Enterobacteriaceae, are one of the most common causes of diarrheal diseases in human worldwide which have become a significant public health burden. So, we aimed to analyze the antimicrobial phenotypes and to elucidate the molecular mechanisms underlying resistance to cephalosporins and fluoroquinolones in Shigella isolates from patients with diarrhea in Shanxi Province.
View Article and Find Full Text PDFThe gut microbiota has been shown critical for mucosal adjuvant activity of cholera toxin (CT), a potent mucosal adjuvant. However, the mechanisms involved remain largely unknown. In this study, we report that depletion of gut bacteria significantly decreased mucosal and systemic Ab responses in mice orally immunized with OVA and CT.
View Article and Find Full Text PDFBackground: How the gut microbiota regulates intestinal homeostasis is not completely clear. Gut microbiota metabolite short-chain fatty acids (SCFAs) have been reported to regulate T-cell differentiation. However, the mechanisms underlying SCFA regulation of T-cell differentiation and function remain to be investigated.
View Article and Find Full Text PDFCell Mol Gastroenterol Hepatol
April 2020
Background & Aims: Regenerating islet-derived protein (REG3γ), an antimicrobial peptide, typically expressed by intestinal epithelial cells (IEC), plays crucial roles in intestinal homeostasis and controlling gut microbiota. However, the mechanisms that regulate IEC expression of REG3γ are still largely unclear. In this study, we investigated whether and how interleukin (IL) 33, an alarmin produced by IEC in response to injury, regulates REG3γ expression in IEC, thus contributing to intestinal homeostasis.
View Article and Find Full Text PDFThe role of retinoid-related orphan receptor γ t (RORγt) in Th17 cell differentiation has been well established; however, how it regulates other T cell lineages is still not clearly understood. In this study, we report that in mice, while promoting Th17 cell differentiation, RORγt inhibited IL-10 production by T cells, thereby preserving the pathogenicity of Th17 cells. Treatment with RORγ-specific inhibitor suppressed Th17 cell signature cytokines, but promoted IL-10 production.
View Article and Find Full Text PDFT-cells are crucial in maintanence of intestinal homeostasis, however, it is still unclear how microbiota metabolites regulate T-effector cells. Here we show gut microbiota-derived short-chain fatty acids (SCFAs) promote microbiota antigen-specific Th1 cell IL-10 production, mediated by G-protein coupled receptors 43 (GPR43). Microbiota antigen-specific Gpr43 CBir1 transgenic (Tg) Th1 cells, specific for microbiota antigen CBir1 flagellin, induce more severe colitis compared with wide type (WT) CBir1 Tg Th1 cells in Rag recipient mice.
View Article and Find Full Text PDFNeutrophils are the first responders to sites of inflammation when the intestinal epithelial barrier is breached and the gut microbiota invade. Despite current efforts in understanding the role of neutrophils in intestinal homeostasis, the complex interactions between neutrophils and intestinal epithelial cells (IECs) is still not well characterized. In this study, we demonstrated that neutrophils enhanced production of amphiregulin (AREG), a member of the EGFR ligand family, by IECs, which promoted IEC barrier function and tissue repair.
View Article and Find Full Text PDFBackground: Brucellosis is a worldwide zoonotic disease caused by Brucella spp. Brucella invades the body through the skin mucosa, digestive tract, and respiratory tract. However, only a few studies on human spontaneous abortion attributable to Brucella have been reported.
View Article and Find Full Text PDFThe antimicrobial peptides (AMP) produced by intestinal epithelial cells (IEC) play crucial roles in the regulation of intestinal homeostasis by controlling microbiota. Gut microbiota has been shown to promote IEC expression of RegIIIγ and certain defensins. However, the mechanisms involved are still not completely understood.
View Article and Find Full Text PDFIt has been shown recently that neutrophils are able to produce IL-22 and IL-17, which differentially regulate the pathogenesis of inflammatory bowel disease. However, it is still largely unknown how the neutrophil production of IL-22 and IL-17 is regulated, and their role in the pathogenesis of inflammatory bowel disease. In this study, we found that IL-23 promoted neutrophil production of IL-17 and IL-22.
View Article and Find Full Text PDFMultiple mechanisms exist in regulation of host responses to massive challenges from microbiota to maintain immune homeostasis in the intestines. Among these is the enriched Th17 cells in the intestines, which regulates intestinal homeostasis through induction of antimicrobial peptides and secretory IgA among others. However, the means by which Th17 cells develop in response to microbiota is still not completely understood.
View Article and Find Full Text PDFIt has been shown that while commensal bacteria promote Th1, Th17 and Treg cells in lamina propria (LP) in steady-state conditions, they suppress mucosal Th2 cells. However, it is still unclear whether there are specific commensal organisms down-regulating Th2 responses, and the mechanism involved. Here we demonstrate that commensal A4 bacteria, a member of the Lachnospiraceae family, which produce an immunodominant microbiota CBir1 antigen, inhibits LP Th2-cell development.
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