scholarly journals The Role of IL-33 in Gut Mucosal Inflammation

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Luca Pastorelli ◽  
Carlo De Salvo ◽  
Maurizio Vecchi ◽  
Theresa T. Pizarro
Keyword(s):  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Experimental Models ◽  
Conclusive Evidence ◽  
The Body ◽  
Lymphoid Cells ◽  
Mucosal Inflammation ◽  
Inflammatory Bowel ◽  
Chronic Intestinal Inflammation

Interleukin (IL)-33 is a recently identified cytokine belonging to the IL-1 family that is widely expressed throughout the body and has the ability to induce Th2 immune responses. In addition, IL-33 plays a key role in promoting host defenses against parasites through the expansion of a novel population of innate lymphoid cells. In recent years, a growing body of evidence has shown that the proinflammatory properties displayed by IL-33 are detrimental in several experimental models of inflammation; in others, however, IL-33 appears to have protective functions. In 2010, four different research groups consistently described the upregulation of IL-33 in patients with inflammatory bowel disease (IBD). Animal models of IBD were subsequently utilized in order to mechanistically determine the precise role of IL-33 in chronic intestinal inflammation, without, however, reaching conclusive evidence demonstrating whether IL-33 is pathogenic or protective. Indeed, data generated from these studies suggest that IL-33 may possess dichotomous functions, enhancing inflammatory responses on one hand and promoting epithelial integrity on the other. This review focuses on the available data regarding IL-33/ST2 in the physiological and inflammatory states of the gut in order to speculate on the possible roles of this novel IL-1 family member in intestinal inflammation.

scholarly journals Going Beyond Bacteria: Uncovering the Role of Archaeome and Mycobiome in Inflammatory Bowel Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Yashar Houshyar ◽  
Luca Massimino ◽  
Luigi Antonio Lamparelli ◽  
Silvio Danese ◽  
Federica Ungaro
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
The Body ◽  
Inflammatory Conditions ◽  
Relapsing Remitting ◽  
Health And Disease ◽  
Inflammatory Bowel ◽  
Chronic Intestinal Inflammation

Inflammatory Bowel Disease (IBD) is a multifaceted class of relapsing-remitting chronic inflammatory conditions where microbiota dysbiosis plays a key role during its onset and progression. The human microbiota is a rich community of bacteria, viruses, fungi, protists, and archaea, and is an integral part of the body influencing its overall homeostasis. Emerging evidence highlights dysbiosis of the archaeome and mycobiome to influence the overall intestinal microbiota composition in health and disease, including IBD, although they remain some of the least understood components of the gut microbiota. Nonetheless, their ability to directly impact the other commensals, or the host, reasonably makes them important contributors to either the maintenance of the mucosal tissue physiology or to chronic intestinal inflammation development. Therefore, the full understanding of the archaeome and mycobiome dysbiosis during IBD pathogenesis may pave the way to the discovery of novel mechanisms, finally providing innovative therapeutic targets that can soon implement the currently available treatments for IBD patients.

scholarly journals Immunopathophysiology of inflammatory bowel disease: how genetics link barrier dysfunction and innate immunity to inflammation

2017 ◽  
Vol 23 (6) ◽  
pp. 497-505 ◽  
Author(s):  
Minesh Mehta ◽  
Shifat Ahmed ◽  
Gerald Dryden
Keyword(s):  
Inflammatory Bowel Disease ◽  
Innate Immunity ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Clinical Symptoms ◽  
Barrier Dysfunction ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Chronic Intestinal Inflammation

Inflammatory bowel diseases (IBD) comprise a distinct set of clinical symptoms resulting from chronic or relapsing immune activation and corresponding inflammation within the gastrointestinal (GI) tract. Diverse genetic mutations, encoding important aspects of innate immunity and mucosal homeostasis, combine with environmental triggers to create inappropriate, sustained inflammatory responses. Recently, significant advances have been made in understanding the interplay of the intestinal epithelium, mucosal immune system, and commensal bacteria as a foundation of the pathogenesis of inflammatory bowel disease. Complex interactions between specialized intestinal epithelial cells and mucosal immune cells determine different outcomes based on the environmental input: the development of tolerance in the presence of commensal bacterial or the promotion of inflammation upon recognition of pathogenic organisms. This article reviews key genetic abnormalities involved in inflammatory and homeostatic pathways that enhance susceptibility to immune dysregulation and combine with environmental triggers to trigger the development of chronic intestinal inflammation and IBD.

scholarly journals IL-23–responsive innate lymphoid cells are increased in inflammatory bowel disease

2011 ◽  
Vol 208 (6) ◽  
pp. 1127-1133 ◽  
Author(s):  
Alessandra Geremia ◽  
Carolina V. Arancibia-Cárcamo ◽  
Myles P.P. Fleming ◽  
Nigel Rust ◽  
Baljit Singh ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Human Intestine ◽  
Health And Disease ◽  
Inflammatory Bowel ◽  
Selective Increase

Results of experimental and genetic studies have highlighted the role of the IL-23/IL-17 axis in the pathogenesis of inflammatory bowel disease (IBD). IL-23–driven inflammation has been primarily linked to Th17 cells; however, we have recently identified a novel population of innate lymphoid cells (ILCs) in mice that produces IL-17, IL-22, and IFN-γ in response to IL-23 and mediates innate colitis. The relevance of ILC populations in human health and disease is currently poorly understood. In this study, we have analyzed the role of IL-23–responsive ILCs in the human intestine in control and IBD patients. Our results show increased expression of the Th17-associated cytokine genes IL17A and IL17F among intestinal CD3− cells in IBD. IL17A and IL17F expression is restricted to CD56− ILCs, whereas IL-23 induces IL22 and IL26 in the CD56+ ILC compartment. Furthermore, we observed a significant and selective increase in CD127+CD56− ILCs in the inflamed intestine in Crohn’s disease (CD) patients but not in ulcerative colitis patients. These results indicate that IL-23–responsive ILCs are present in the human intestine and that intestinal inflammation in CD is associated with the selective accumulation of a phenotypically distinct ILC population characterized by inflammatory cytokine expression. ILCs may contribute to intestinal inflammation through cytokine production, lymphocyte recruitment, and organization of the inflammatory tissue and may represent a novel tissue-specific target for subtypes of IBD.

scholarly journals OP37 Fibrogenesis in chronic DSS colitis is driven by an innate lymphoid cell-independent innate immune response

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S038-S039
Author(s):  
B Creyns ◽  
J Cremer ◽  
G De Hertogh ◽  
L Boon ◽  
M Ferrante ◽  
...  
Keyword(s):  
Lamina Propria ◽  
Intestinal Inflammation ◽  
Muscularis Propria ◽  
Lymphoid Cells ◽  
Blue Staining ◽  
Human Organ ◽  
Dss Colitis ◽  
Rag 1 ◽  
Chronic Intestinal Inflammation

Abstract Background Obtaining insights in the pathogenesis of intestinal fibrosis is a priority for improving outcomes in inflammatory bowel diseases (IBD). Studies in murine models and human organ fibrosis indicate a role for innate immunity pathways in fibrosis. The aim of this study was to dissect the role of innate lymphoid cells (ILC) in chronic intestinal inflammation and fibrosis. Methods A chronic 3-cycles dextran sulphate sodium (DSS) model was induced in wild-type (WT), recombinant activating gene (RAG)-deficient (lacking adaptive immunity), RAG−/− common γ-chain (ɣc)−/− (lacking ILC) and anti-CD90.2 treated (ILC depleted) C57Bl/6 RAG−/− mice. One cycle of DSS comprised 1 week of DSS administration followed by 2 weeks of recovery with normal drinking water. Colonic lamina propria cells were isolated and CD45+Lineage−CD127+CD90.2+ ILC, Ly6C+ monocytes and Ly6G+ neutrophils were identified after staining by flow cytometry. Inflammation and fibrosis were scored by macroscopic and HE and Martius Scarlet Blue staining and fibrosis was evaluated by hydroxyproline quantification. For analysis Kruskal–Wallis testing with multiple Dunn’s comparisons was performed. Results In RAG-1−/− mice chronic inflammation and fibrosis developed similarly as in WT mice, with elevated KLRG-1+ ILC2 (68.90 vs. 48.00% of ILC, p = 0.012) after repeated DSS exposure as compared with control mice (Figure 1). Chronic colitis could also be induced in RAG−/−ɣc−/− or ILC depleted RAG−/− mice (ILC: 0.99 vs. 25.70% of CD45+ cells, p = 0.029), with no attenuation of fibrosis (p > 0.99) as compared with chronic DSS exposed RAG-1−/− mice despite the absence of ILC (Figure 2). Colon length decrease was more pronounced in RAG−/−yc−/− as compared with RAG-1−/− mice after chronic DSS colitis (7.15 vs. 8.30 cm, p = 0.046), while hydroxyproline levels and thickness of mucosa and muscularis propria were not different in RAG−/−yc−/− as compared with RAG-1−/− mice after chronic DSS. Moreover, after the second cycle of DSS a slower recovery of weight was seen in RAG−/−yc−/− mice as compared with RAG-1−/− mice (d31: 88.64 vs. 111.0% of initial weight, p < 0.001; d35 p = 0.001; d39 p = 0.006 and d42 p = 0.002) (Figure 3). In absence of ILC, RAG−/−yc−/− mice increased lamina propria neutrophils (19.10 vs. 5.91% of CD45+ cells, p = 0.004) and monocytes (11.80 vs. 3.25% of CD45+ cells, p = 0.004) may represent an alternative source of inflammation. Conclusion These data argue against a pro-fibrotic role of ILC in the induction of fibrosis in chronic DSS colitis, and suggest a protective and recovery-enhancing role of ILC after repeated intestinal injury.

Ultrasensitive molecular imaging of intestinal mucosal inflammation using leukocyte-mimicking particles targeted to MAdCAM-1 in mice

2020 ◽  
Vol 12 (560) ◽  
pp. eaaz4047
Author(s):  
Antoine P. Fournier ◽  
Sara Martinez de Lizarrondo ◽  
Adrien Rateau ◽  
Axel Gerard-Brisou ◽  
Maximilian J. Waldner ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Intestinal Mucosa ◽  
Inflammatory Bowel Diseases ◽  
Intestinal Inflammation ◽  
Mucosal Inflammation ◽  
Molecular Mri ◽  
Mucosal Tissues ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Chronic Intestinal Inflammation

Mucosal tissues play critical roles in health and disease as the primary barrier between the external world and the inner body, lining the digestive, respiratory, urinary, mammary, and reproductive tracts. Clinical evaluation of mucosal tissues is currently performed using endoscopy, such as ileocolonoscopy for the intestinal mucosa, which causes substantial patient discomfort and can lead to organ damage. Here, we developed a contrast agent for molecular magnetic resonance imaging (MRI) that is targeted to mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1), an adhesion molecule overexpressed by inflamed mucosal tissues. We investigated the diagnostic performance of molecular MRI of MAdCAM-1 to detect mucosal inflammation in several models of acute and chronic intestinal inflammation in mice. We demonstrated that molecular MRI of MAdCAM-1 reveals disease activity and can evaluate the response to inflammatory treatments along the whole intestinal mucosa in clinically relevant models of inflammatory bowel diseases. We also provide evidence that this technique can detect low, subclinical mucosal inflammation. Molecular MRI of MAdCAM-1 has potential applications in early diagnosis, longitudinal follow-up, and therapeutic response monitoring in diseases affecting mucosal tissues, such as inflammatory bowel diseases.

scholarly journals The Role of Cytokines in Inflammatory Bowel Disease

1994 ◽  
Vol 3 (1) ◽  
pp. 3-9 ◽  
Author(s):  
G. Radford-Smith ◽  
D. P. Jewell
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Intestinal Inflammation ◽  
Inflammatory Lesions ◽  
Immunoregulatory Cytokines ◽  
Current Thinking ◽  
Inflammatory Bowel ◽  
Chronic Intestinal Inflammation ◽  
Th1 And Th2

Cytokines play an important role in the development and persistence of the inflammatory lesions seen in Crohn's disease and ulcerative colitis. This review discusses the current thinking of the role of cytokines in chronic intestinal inflammation including the involvement of immunoregulatory cytokines within the Th1 and Th2 subsets.

scholarly journals IL-1β mediates chronic intestinal inflammation by promoting the accumulation of IL-17A secreting innate lymphoid cells and CD4+ Th17 cells

2012 ◽  
Vol 209 (9) ◽  
pp. 1595-1609 ◽  
Author(s):  
Margherita Coccia ◽  
Oliver J. Harrison ◽  
Chris Schiering ◽  
Mark J. Asquith ◽  
Burkhard Becher ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Intestinal Pathology ◽  
Bowel Diseases ◽  
Chronic Intestinal Inflammation

Although very high levels of interleukin (IL)-1β are present in the intestines of patients suffering from inflammatory bowel diseases (IBD), little is known about the contribution of IL-1β to intestinal pathology. Here, we used two complementary models of chronic intestinal inflammation to address the role of IL-1β in driving innate and adaptive pathology in the intestine. We show that IL-1β promotes innate immune pathology in Helicobacter hepaticus–triggered intestinal inflammation by augmenting the recruitment of granulocytes and the accumulation and activation of innate lymphoid cells (ILCs). Using a T cell transfer colitis model, we demonstrate a key role for T cell–specific IL-1 receptor (IL-1R) signals in the accumulation and survival of pathogenic CD4+ T cells in the colon. Furthermore, we show that IL-1β promotes Th17 responses from CD4+ T cells and ILCs in the intestine, and we describe synergistic interactions between IL-1β and IL-23 signals that sustain innate and adaptive inflammatory responses in the gut. These data identify multiple mechanisms through which IL-1β promotes intestinal pathology and suggest that targeting IL-1β may represent a useful therapeutic approach in IBD.

scholarly journals Innate Lymphoid Cells in Intestinal Homeostasis and Inflammatory Bowel Disease

2021 ◽  
Vol 22 (14) ◽  
pp. 7618
Author(s):  
Angela Saez ◽  
Raquel Gomez-Bris ◽  
Beatriz Herrero-Fernandez ◽  
Claudia Mingorance ◽  
Cristina Rius ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cells ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Intestinal Homeostasis ◽  
Mucosal Homeostasis ◽  
Inflammatory Bowel ◽  
Chronic Intestinal Inflammation

Inflammatory bowel disease (IBD) is a heterogeneous state of chronic intestinal inflammation of unknown cause encompassing Crohn’s disease (CD) and ulcerative colitis (UC). IBD has been linked to genetic and environmental factors, microbiota dysbiosis, exacerbated innate and adaptive immunity and epithelial intestinal barrier dysfunction. IBD is classically associated with gut accumulation of proinflammatory Th1 and Th17 cells accompanied by insufficient Treg numbers and Tr1 immune suppression. Inflammatory T cells guide innate cells to perpetuate a constant hypersensitivity to microbial antigens, tissue injury and chronic intestinal inflammation. Recent studies of intestinal mucosal homeostasis and IBD suggest involvement of innate lymphoid cells (ILCs). These lymphoid-origin cells are innate counterparts of T cells but lack the antigen receptors expressed on B and T cells. ILCs play important roles in the first line of antimicrobial defense and contribute to organ development, tissue protection and regeneration, and mucosal homeostasis by maintaining the balance between antipathogen immunity and commensal tolerance. Intestinal homeostasis requires strict regulation of the quantity and activity of local ILC subpopulations. Recent studies demonstrated that changes to ILCs during IBD contribute to disease development. A better understanding of ILC behavior in gastrointestinal homeostasis and inflammation will provide valuable insights into new approaches to IBD treatment. This review summarizes recent research into ILCs in intestinal homeostasis and the latest advances in the understanding of the role of ILCs in IBD, with particular emphasis on the interaction between microbiota and ILC populations and functions.

The role of macrophages in inflammatory bowel diseases

2009 ◽  
Vol 11 ◽  
Author(s):  
Sigrid E.M. Heinsbroek ◽  
Siamon Gordon
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Inflammatory Responses ◽  
Intestinal Flora ◽  
The Body ◽  
Intestinal Immunity ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Intestinal Macrophage ◽  
Small And Large Intestine

The small and large intestine contain the largest number of macrophages in the body and these cells are strategically located directly underneath the epithelial layer, enabling them to sample the lumen. Such intestinal macrophages have a different phenotype from other tissue macrophages in that they ingest and may kill microbes but they do not mediate strong pro-inflammatory responses upon microbial recognition. These properties are essential for maintaining a healthy intestine. It is generally accepted that tolerance to the intestinal flora is lost in inflammatory bowel diseases, and genes involved in microbial recognition, killing and macrophage activation have already been associated with these diseases. In this review, we shed light on the intestinal macrophage and how it influences intestinal immunity.

scholarly journals The Enteric Nervous System and the Microenvironment of the Gut: The Translational Aspects of the Microbiome-Gut-Brain Axis

2021 ◽  
Vol 11 (24) ◽  
pp. 12000
Author(s):  
Fruzsina Mogor ◽  
Tamás Kovács ◽  
Zoltan Lohinai ◽  
David Dora
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Intestinal Inflammation ◽  
Waste Products ◽  
Close Cooperation ◽  
Inflammatory Bowel ◽  
External Stimuli ◽  
Chronic Intestinal Inflammation ◽  
Molecular Crosstalk

The proper functioning of the gastrointestinal tract is essential for digestion, absorption and the elimination of waste products. It protects us against pathogens, allergens and toxins, continuously monitoring and regulating the internal environment. The vast majority of these tasks are carried out by the nervous and immune systems of the gut in close cooperation by constantly adapting to internal and external stimuli, maintaining its homeostasis. In this review, we would like to summarize the most recent findings about the cytoarchitecture and functional microanatomy of the enteric nervous system and the immune microenvironment of the gut highlighting the essential role and inevitable molecular crosstalk between these two highly organized networks. Gut neuroimmunology is a rapidly evolving field and might help us to understand the etiology of inflammatory bowel disease and the systemic consequences of chronic intestinal inflammation. Finally, we also included a brief outlook to present the most recent research depicting the multifaceted role of the gut microbiome, its contribution to the gut-brain axis and human disease.

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