The Role of Immune and Epithelial Stem Cells in Inflammatory Bowel Disease Therapy

2020 ◽  
Vol 21 (14) ◽  
pp. 1405-1416 ◽  
Author(s):  
Agata Binienda ◽  
Sylwia Ziolkowska ◽  
Ingvild H. Hauge ◽  
Maciej Salaga
Keyword(s):  
Inflammatory Bowel Disease ◽  
Stem Cells ◽  
Bowel Disease ◽  
Lymphoid Cells ◽  
Interleukin 12 ◽  
Epithelial Stem Cells ◽  
Significant Deterioration ◽  
Hematopoietic Stem ◽  
Inflammatory Bowel

Background: Inflammatory Bowel Disease (IBD) is categorized as Crohn’s disease (CD) and Ulcerative colitis (UC) and is characterized by chronic inflammation in the gastrointestinal (GI) tract. Relapsing symptoms, including abdominal pain, increased stool frequency, loss of appetite as well as anemia contribute to significant deterioration of quality of life. IBD treatment encompasses chemotherapy (e.g. corticosteroids, thiopurines) and biological agents (e.g. antibodies targeting tumour necrosis factor α, interleukin 12/23) and surgery. However, efficacy of these therapies is not satisfactory. Thus, scientists are looking for new options in IBD treatment that could induce and maintain remission. Objective: To summarize previous knowledge about role of different intestinal cells in IBD pathophysiology and application of stem cells in the IBD treatment. Results: Recent studies have emphasized an important role of innate lymphoid cells (ILCs) as well as intestinal epithelial cells (IECs) in the IBD pathophysiology suggesting that these types of cells can be new targets for IBD treatment. Moreover, last studies show that stem cells transplantation reduces inflammation in patients suffering from IBD, which are resistant to conventional therapies. Conclusion: Both hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) are able to restore damaged tissue and regulate the immune system. Autologous HSCs transplantation eliminates autoreactive cells and replace them with new T-cells resulting a long-time remission. Whereas MSCs transplantation is effective therapy in one of the major complications of IBD, perianal fistulas.

scholarly journals The role of adipose stem cells in inflammatory bowel disease: From biology to novel therapeutic strategies

2016 ◽  
Vol 17 (9) ◽  
pp. 889-898 ◽  
Author(s):  
Francesco De Francesco ◽  
Maurizio Romano ◽  
Laura Zarantonello ◽  
Cesare Ruffolo ◽  
Daniele Neri ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Stem Cells ◽  
Bowel Disease ◽  
Therapeutic Strategies ◽  
Adipose Stem Cells ◽  
Inflammatory Bowel ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

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.

The IL-12/23/STAT Axis as a Therapeutic Target in Inflammatory Bowel Disease: Mechanisms and Evidence in Man

2015 ◽  
Vol 33 (Suppl. 1) ◽  
pp. 113-119 ◽  
Author(s):  
Irene Marafini ◽  
Erika Angelucci ◽  
Francesco Pallone ◽  
Giovanni Monteleone
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Interferon Γ ◽  
Cell Polarization ◽  
Lymphoid Cells ◽  
Inflammatory Cytokine Response ◽  
Inflammatory Bowel ◽  
The Common ◽  
Necrosis Factor

Background: In inflamed tissues of patients with inflammatory bowel disease (IBD), many immune and non-immune cells produce a vast array of cytokines, which contribute to expand and maintain the pathologic process. Key Message: Interleukin (IL)-12 and IL-23, 2 heterodimeric cytokines sharing the common p40 subunit, are over-produced in IBD and supposed to play a major role in promoting and/or sustaining the pro-inflammatory cytokine response in these disorders. IL-12 targets mostly T cells and innate lymphoid cells and through activation of Stat4 promotes T helper (Th)1 cell polarization, interferon-γ and IL-21 production, while IL-23 activates Stat3 thus amplifying Th17 cell programs. These observations together with the demonstration that IL-12 and IL-23 drive pathogenic responses in animal models of colitis have paved the way for the development of IL-12p40 blockers. Two monoclonal antibodies (ustekinumab and briakinumab) targeting p40 have been tested in Crohn's disease (CD) patients. Blockade of IL-12p40 is beneficial in CD patients resistant to tumor necrosis factor (TNF) antagonists and promotes resolution of psoriatic lesions that develop in IBD patients following anti-TNF therapy. Conclusions: The available human data support the pathogenic role of IL-12/IL-23 in IBD and suggest that IL-12p40 blockers could help manage some subsets of IBD patients.

Persistence of Lgr5+ colonic epithelial stem cells in mouse models of inflammatory bowel disease

2021 ◽  
Author(s):  
Nandini Girish ◽  
Cambrian Y Liu ◽  
Safina Gadeock ◽  
Marie L Gomez ◽  
Ying Huang ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Stem Cells ◽  
Mouse Models ◽  
T Cell Activation ◽  
Bowel Disease ◽  
Cell Activation ◽  
Healing Process ◽  
Severe Exacerbation ◽  
Epithelial Stem Cells ◽  
Inflammatory Bowel

Intestinal mucosal healing is the primary therapeutic goal of medical treatments for inflammatory bowel disease (IBD). Epithelial stem cells are key players in the healing process. Lgr5+ stem cells maintain cellular turnover during homeostasis in the colonic crypt. However, they are lost and dispensable for repair in a wide variety of injury models, including dextran sulfate sodium (DSS) colitis, radiation, helminth infection, and T-cell activation. The direct loss of Lgr5+ cells activates a plasticity response in the epithelium in which other cell types can serve as stem cells. Whether this paradigm applies to mouse models of IBD remains unknown. In contrast to previously tested models, IBD models involve an inflammatory response rooted in the loss of immunologic tolerance to intestinal luminal contents including the microbiome. Here we show the persistence of Lgr5+ cells in oxazolone, TNBS, and Il10-/- and Il10-/- Tnfr1-/- IBD models. This contrasts with results obtained from DSS-induced injury. Through high-throughput expression profiling, we find that these colitis models were associated with distinct patterns of cytokine expression. Direct exposure of colonic epithelial organoids to DSS, oxazolone, or TNBS resulted in increased apoptosis and loss of Lgr5+ cells. Targeted ablation of Lgr5+ cells resulted in severe exacerbation of chronic, antibody-induced IL-10-deficient colitis, but had only modest effects in TNBS-induced colitis. These results show that distinct mouse models of IBD-like colitis induce different patterns of Lgr5+ stem cell retention and function.

The role of osteopontin (OPN/SSP1) gene variants in inflammatory bowel disease

2009 ◽  
Vol 47 (09) ◽  
Author(s):  
J Glas ◽  
J Seiderer ◽  
HP Török ◽  
B Göke ◽  
T Ochsenkühn ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Gene Variants ◽  
Inflammatory Bowel

Nutrition in inflammatory bowel disease

2009 ◽  
Vol 150 (18) ◽  
pp. 839-845 ◽  
Author(s):  
János Banai
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Fast Food ◽  
Optimal Growth ◽  
Developed Countries ◽  
Aetiological Factor ◽  
Artificial Nutrition ◽  
Food Preservatives ◽  
Inflammatory Bowel

Aetiology of inflammatory bowel disease (IBD) is complex and probably multifactorial. Nutrition has been proposed to be an important aetiological factor for development of IBD. Several components of the diet (such as sugar, fat, fibre, fruit and vegetable, protein, fast food, preservatives etc.) were examined as possible causative agents for IBD. According to some researchers infant feeding (breast feeding) may also contribute to the development of IBD. Though the importance of environmental factors is evidenced by the increasing incidence in developed countries and in migrant population in recent decades, the aetiology of IBD remained unclear. There are many theories, but as yet no dietary approaches have been proved to reduce the risk of developing IBD. The role of nutrition in the management of IBD is better understood. The prevention and correction of malnutrition, the provision of macro- and micronutrients and vitamins and the promotion of optimal growth and development of children are key points of nutritional therapy. In active disease, the effective support of energy and nutrients is a very important part of the therapy. Natural and artificial nutrition or the combination of two can be choosen for supporting therapy of IBD. The author summarises the aetiological and therapeutic role of nutrition in IBD.

scholarly journals Tu1789 – Treatment Response to Ustekinumab and Vedolizumab in Inflammatory Bowel Disease: the Predictive Role of Gut Microbiota

2019 ◽  
Vol 156 (6) ◽  
pp. S-1124
Author(s):  
Clara Caenepeel ◽  
Sara Vieira-Silva ◽  
Jorge F. Vázquez-Castellanos ◽  
Bram Verstockt ◽  
Marc Ferrante ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Gut Microbiota ◽  
Treatment Response ◽  
Bowel Disease ◽  
Predictive Role ◽  
Inflammatory Bowel

scholarly journals The role of heme oxygenase and carbon monoxide in inflammatory bowel disease

Redox Report ◽  
2010 ◽  
Vol 15 (5) ◽  
pp. 193-201 ◽  
Author(s):  
Tomohisa Takagi ◽  
Yuji Naito ◽  
Kazuhiko Uchiyama ◽  
Toshikazu Yoshikawa
Keyword(s):  
Inflammatory Bowel Disease ◽  
Carbon Monoxide ◽  
Heme Oxygenase ◽  
Bowel Disease ◽  
Inflammatory Bowel

Ethnic Differences in the Smoking-Related Risk of Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

2021 ◽  
Author(s):  
Daniele Piovani ◽  
Claudia Pansieri ◽  
Soumya R R Kotha ◽  
Amanda C Piazza ◽  
Celia-Louise Comberg ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Latin American ◽  
Bowel Disease ◽  
Meta Analysis ◽  
Study Data ◽  
Future Research ◽  
Related Risk ◽  
Increased Risk ◽  
Inflammatory Bowel

Abstract Background and aims The association between smoking and inflammatory bowel disease (IBD) relies on old meta-analyses including exclusively non-Jewish White populations. Uncertainty persists regarding the role of smoking in other ethnicities. Methods We systematically searched Medline/PubMed, Embase and Scopus for studies examining tobacco smoking and the risk of developing IBD, i.e., Crohn’s disease (CD) or ulcerative colitis (UC). Two authors independently extracted study data and assessed each study’s risk-of-bias. We examined heterogeneity and small-study effect, and calculated summary estimates using random-effects models. Stratified analyses and meta-regression were employed to study the association between study-level characteristics and effect estimates. The strength of epidemiological evidence was assessed through prespecified criteria. Results We synthesized 57 studies examining the smoking-related risk of developing CD and UC. Non-Jewish White smokers were at increased risk of CD (29 studies; RR: 1.95, 95% CI: 1.69‒2.24; moderate evidence). No association was observed in Asian, Jewish and Latin-American populations (11 studies; RR: 0.97; 95% CI: 0.83–1.13), with no evidence of heterogeneity across these ethnicities. Smokers were at reduced risk of UC (51 studies; RR: 0.55, 95% CI: 0.48–0.64; weak evidence) irrespectively of ethnicity; however, cohort studies, large studies and those recently published showed attenuated associations. Conclusions This meta-analysis did not identify any increased risk of CD in smokers in ethnicities other than non-Jewish Whites, and confirmed the protective effect of smoking on UC occurrence. Future research should characterize the genetic background of CD patients across different ethnicities to improve our understanding on the role of smoking in CD pathogenesis.

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