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Open accessJournal ArticleDOI: 10.3389/FCELL.2021.625423

Roles of Macrophages in the Development and Treatment of Gut Inflammation.

02 Mar 2021-Frontiers in Cell and Developmental Biology (Frontiers Media SA)-Vol. 9, pp 625423-625423
Abstract: Macrophages, which are functional plasticity cells, have the ability to phagocytize and digest foreign substances and acquire pro-(M1-like) or anti-inflammatory (M2-like) phenotypes according to their microenvironment. The large number of macrophages in the intestinal tract, play a significant role in maintaining the homeostasis of microorganisms on the surface of the intestinal mucosa and in the continuous renewal of intestinal epithelial cells. They are not only responsible for innate immunity, but also participate in the development of intestinal inflammation. A clear understanding of the function of macrophages, as well as their role in pathogens and inflammatory response, will delineate the next steps in the treatment of intestinal inflammatory diseases. In this review, we discuss the origin and development of macrophages and their role in the intestinal inflammatory response or infection. In addition, the effects of macrophages in the occurrence and development of inflammatory bowel disease (IBD), and their role in inducing fibrosis, activating T cells, reducing colitis, and treating intestinal inflammation were also reviewed in this paper.

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Topics: Intestinal mucosa (68%), Innate immune system (56%), Inflammation (55%) ... show more
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5 results found


Open accessJournal ArticleDOI: 10.3390/CELLS10081891
26 Jul 2021-Cells
Abstract: The first formal description of the microbicidal activity of extracellular traps (ETs) containing DNA occurred in neutrophils in 2004. Since then, ETs have been identified in different populations of cells involved in both innate and adaptive immune responses. Much of the knowledge has been obtained from in vitro or ex vivo studies; however, in vivo evaluations in experimental models and human biological materials have corroborated some of the results obtained. Two types of ETs have been described-suicidal and vital ETs, with or without the death of the producer cell. The studies showed that the same cell type may have more than one ETs formation mechanism and that different cells may have similar ETs formation mechanisms. ETs can act by controlling or promoting the mechanisms involved in the development and evolution of various infectious and non-infectious diseases, such as autoimmune, cardiovascular, thrombotic, and neoplastic diseases, among others. This review discusses the presence of ETs in neutrophils, macrophages, mast cells, eosinophils, basophils, plasmacytoid dendritic cells, and recent evidence of the presence of ETs in B lymphocytes, CD4+ T lymphocytes, and CD8+ T lymphocytes. Moreover, due to recently collected information, the effect of ETs on COVID-19 is also discussed.

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Topics: Immune system (52%)

2 Citations


Open accessJournal ArticleDOI: 10.3389/FIMMU.2021.768957
Abstract: Immune checkpoint inhibitors (ICIs) have provided tremendous clinical benefit in several cancer types. However, systemic activation of the immune system also leads to several immune-related adverse events. Of these, ICI-mediated colitis (IMC) occurs frequently and is the one with the highest absolute fatality. To improve current treatment strategies, it is important to understand the cellular mechanisms that induce this form of colitis. In this review, we discuss important pathways that are altered in IMC in mouse models and in human colon biopsy samples. This reveals a complex interplay between several types of immune cells and the gut microbiome. In addition to a mechanistic understanding, patients at risk should be identifiable before ICI therapy. Here we propose to focus on T-cell subsets that interact with bacteria after inducing epithelial damage. Especially, intestinal resident immune cells are of interest. This may lead to a better understanding of IMC and provides opportunities for prevention and management.

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Topics: Immune system (52%), Colitis (50%)

Open accessJournal ArticleDOI: 10.2147/JIR.S327609
Abstract: Inflammatory bowel disease (IBD), which affects about 7 million people globally, is a chronic inflammatory condition of the gastrointestinal tract caused by gut microbiota alterations, immune dysregulation, and genetic and environmental factors. The association of microbial and immune molecules with mucin-type O-glycans has been increasingly noticed by researchers. Mucin is the main component of mucus, which forms a protective barrier between the microbiota and immune cells in the colon. Mucin-type O-glycans alter the diversity of gastrointestinal microorganisms, which in turn increases the level of O-glycosylation of host intestinal proteins via the utilization of glycans. Additionally, alterations in mucin-type O-glycans not only increase the activity and stability of immune cells but are also involved in the maintenance of intestinal mucosal immune tolerance. Although there is accumulating evidence indicating that mucin-type O-glycans play an important role in IBD, there is limited literature that integrates available data to present a complete picture of exactly how O-glycans affect IBD. This review emphasizes the roles of the mucin-type O-glycans in IBD. This seeks to provide a better understanding and encourages future studies on IBD glycosylation and the design of novel glycan-inspired therapies for IBD.

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Topics: Immune dysregulation (60%), Gut flora (57%), Immune system (53%) ... show more

Open accessJournal ArticleDOI: 10.3389/FIMMU.2021.740565
Lianlian Tian1, Jun-Long Zhao1, Jian-Qin Kang1, Shibo Guo1  +6 moreInstitutions (1)
Abstract: Inflammatory bowel disease (IBD) is characterized by chronic and relapsing intestinal inflammation, which currently lacks safe and effective medicine. Some previous studies indicated that Astragaloside IV (AS-IV), a natural saponin extracted from the traditional Chinese medicine herb Ligusticum chuanxiong, alleviates the experimental colitis symptoms in vitro and in vivo. However, the mechanism of AS-IV on IBD remains unclear. Accumulating evidence suggests that M2-polarized intestinal macrophages play a pivotal role in IBD progression. Here, we found that AS-IV attenuated clinical activity of DSS-induced colitis that mimics human IBD and resulted in the phenotypic transition of macrophages from immature pro-inflammatory macrophages to mature pro-resolving macrophages. In vitro, the phenotype changes of macrophages were observed by qRT-PCR after bone marrow-derived macrophages (BMDMs) were induced to M1/M2 and incubated with AS-IV, respectively. In addition, AS-IV was effective in inhibiting pro-inflammatory macrophages and promoting the pro-resolving macrophages to ameliorate experimental colitis via the regulation of the STAT signaling pathway. Hence, we propose that AS-IV can ameliorate experimental colitis partially by modulating macrophage phenotype by remodeling the STAT signaling, which seems to have an essential function in the ability of AS-IV to alleviate the pathological progress of IBD.

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Topics: Macrophage polarization (58%), Colitis (55%), Inflammatory bowel disease (53%) ... show more

Open accessJournal ArticleDOI: 10.3390/PH14040299
Abstract: Inflammatory bowel disease is a chronic relapsing disease. Multiple factors can cause inflammatory bowel disease (IBD), including diet, imbalance of the immune system, and impaired intestinal barrier function. Type 2 diabetes mellitus is a complex and chronic metabolic disease caused by a combination of insulin resistance and an ineffective insulin secretory response. The co-occurrence of these two diseases, demonstrating interrelated effects within the gut microbiota, has been frequently reported. This study evaluated the effects of a fermented glycated conjugate of whey protein and galactose with Lactobacillus gasseri 4M13 (FMRP) to prevent type 2 diabetes mellitus with inflammatory bowel disease. C57BLKS/J- db/db mice were orally administered FMRP for 14 consecutive days and 2% dextran sulfate sodium (DSS) in water ad libitum for 5 days to induce colitis. FMRP-fed mice showed improved insulin secretion and symptoms of colitis. Compared to the DSS group, the FMRP group showed a decreased abundance of six bacterial genera and increased abundance of Alistipes and Hungateiclostridium. In cecal contents, the levels of short-chain fatty acids increased in the FMRP group compared to those in the DSS group. Continuous administration of FMRP thus may improve the homeostasis of not only insulin secretion and inflammation, but also the intestinal environment in inflammatory bowel disease and type 2 diabetes mellitus.

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Topics: Inflammatory bowel disease (59%), Gut flora (57%), Insulin resistance (56%) ... show more
References
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202 results found


Open accessJournal ArticleDOI: 10.1038/NRI2448
David M. Mosser1, Justin P. Edwards1Institutions (1)
Abstract: Macrophages display remarkable plasticity and can change their physiology in response to environmental cues. These changes can give rise to different populations of cells with distinct functions. In this Review we suggest a new grouping of macrophage populations based on three different homeostatic activities - host defence, wound healing and immune regulation. We propose that similarly to primary colours, these three basic macrophage populations can blend into various other 'shades' of activation. We characterize each population and provide examples of macrophages from specific disease states that have the characteristics of one or more of these populations.

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Topics: Regulatory macrophages (59%), Macrophage polarization (57%), M2 Macrophage (55%) ... show more

6,350 Citations


Journal ArticleDOI: 10.1016/J.IT.2004.09.015
Abstract: Plasticity and functional polarization are hallmarks of the mononuclear phagocyte system. Here we review emerging key properties of different forms of macrophage activation and polarization (M1, M2a, M2b, M2c), which represent extremes of a continuum. In particular, recent evidence suggests that differential modulation of the chemokine system integrates polarized macrophages in pathways of resistance to, or promotion of, microbial pathogens and tumors, or immunoregulation, tissue repair and remodeling.

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Topics: Macrophage polarization (62%), M2 Macrophage (55%), Regulatory macrophages (53%) ... show more

4,902 Citations


Open accessJournal ArticleDOI: 10.1073/PNAS.0706625104
Abstract: The two primary human inflammatory bowel diseases, Crohn's disease (CD) and ulcerative colitis (UC), are idiopathic relapsing disorders characterized by chronic inflammation of the intestinal tract. Although several lines of reasoning suggest that gastrointestinal (GI) microbes influence inflammatory bowel disease (IBD) pathogenesis, the types of microbes involved have not been adequately described. Here we report the results of a culture-independent rRNA sequence analysis of GI tissue samples obtained from CD and UC patients, as well as non-IBD controls. Specimens were obtained through surgery from a variety of intestinal sites and included both pathologically normal and abnormal states. Our results provide comprehensive molecular-based analysis of the microbiota of the human small intestine. Comparison of clone libraries reveals statistically significant differences between the microbiotas of CD and UC patients and those of non-IBD controls. Significantly, our results indicate that a subset of CD and UC samples contained abnormal GI microbiotas, characterized by depletion of commensal bacteria, notably members of the phyla Firmicutes and Bacteroidetes. Patient stratification by GI microbiota provides further evidence that CD represents a spectrum of disease states and suggests that treatment of some forms of IBD may be facilitated by redress of the detected microbiological imbalances.

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3,454 Citations


Journal ArticleDOI: 10.1038/NATURE06005
26 Jul 2007-Nature
Abstract: Recently, substantial advances in the understanding of the molecular pathogenesis of inflammatory bowel disease (IBD) have been made owing to three related lines of investigation. First, IBD has been found to be the most tractable of complex disorders for discovering susceptibility genes, and these have shown the importance of epithelial barrier function, and innate and adaptive immunity in disease pathogenesis. Second, efforts directed towards the identification of environmental factors implicate commensal bacteria (or their products), rather than conventional pathogens, as drivers of dysregulated immunity and IBD. Third, murine models, which exhibit many of the features of ulcerative colitis and seem to be bacteria-driven, have helped unravel the pathogenesis/mucosal immunopathology of IBD.

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3,452 Citations


Open accessJournal ArticleDOI: 10.1016/J.IMMUNI.2014.06.008
17 Jul 2014-Immunity
Abstract: Description of macrophage activation is currently contentious and confusing. Like the biblical Tower of Babel, macrophage activation encompasses a panoply of descriptors used in different ways. The lack of consensus on how to define macrophage activation in experiments in vitro and in vivo impedes progress in multiple ways, including the fact that many researchers still consider there to be only two types of activated macrophages, often termed M1 and M2. Here, we describe a set of standards encompassing three principles—the source of macrophages, definition of the activators, and a consensus collection of markers to describe macrophage activation—with the goal of unifying experimental standards for diverse experimental scenarios. Collectively, we propose a common framework for macrophage-activation nomenclature.

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Topics: Macrophage polarization (53%)

3,340 Citations


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