TIPE2 Promotes Tumor Initiation But Inhibits Tumor Progression in Murine Colitis-Associated Colon Cancer

2021 ◽  
Author(s):  
Zienab Etwebi ◽  
Jason R Goldsmith ◽  
Mayassa Bou-Dargham ◽  
Yuhua Tian ◽  
Ryan Hood ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Colon Cancer ◽  
Tumor Progression ◽  
Immune Cells ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Suppressor Cells ◽  
The United States ◽  
Inflammatory Bowel ◽  
Chronic Intestinal Inflammation

Abstract Background Colorectal cancer (CRC) is the third leading cause of cancer in the United States, and inflammatory bowel disease patients have an increased risk of developing CRC due to chronic intestinal inflammation with it being the cause of death in 10% to 15% of inflammatory bowel disease patients. TIPE2 (TNF-alpha-induced protein 8-like 2) is a phospholipid transporter that is highly expressed in immune cells and is an important regulator of immune cell function. Methods The azoxymethane/dextran sulfate sodium murine model of colitis-associated colon cancer (CAC) was employed in Tipe2 –/– and wild-type mice, along with colonoid studies, to determine the role of TIPE2 in CAC. Results Early on, loss of TIPE2 led to significantly less numbers of visible tumors, which was in line with its previously described role in myeloid-derived suppressor cells. However, as time went on, loss of TIPE2 promoted tumor progression, with larger tumors appearing in Tipe2 –/– mice. This was associated with increased interleukin-22/STAT3 phosphorylation signaling. Similar effects were also observed in primary colonoid cultures, together demonstrating that TIPE2 also directly regulated colonocytes in addition to immune cells. Conclusions This work demonstrates that TIPE2 has dual effects in CAC. In the colonocytes, it works as a tumor suppressor. However, in the immune system, TIPE2 may promote tumorigenesis through suppressor cells or inhibit it through IL-22 secretion. Going forward, this work suggests that targeting TIPE2 for CRC therapy requires cell- and pathway-specific approaches and serves as a cautionary tale for immunotherapy approaches in general in terms of colon cancer, as intestinal inflammation can both promote and inhibit cancer.

Immunological Regulation of Intestinal Fibrosis in Inflammatory Bowel Disease

2021 ◽  
Author(s):  
Giorgos Bamias ◽  
Theresa T Pizarro ◽  
Fabio Cominelli
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Large Scale ◽  
Intestinal Inflammation ◽  
Temporal Association ◽  
Stricture Formation ◽  
Intestinal Fibrosis ◽  
Matrix Deposition ◽  
Inflammatory Bowel ◽  
Chronic Intestinal Inflammation

Abstract Intestinal fibrosis is a late-stage phenotype of inflammatory bowel disease (IBD), which underlies most of the long-term complications and surgical interventions in patients, particularly those with Crohn’s disease. Despite these issues, antifibrotic therapies are still scarce, mainly due to the current lack of understanding concerning the pathogenetic mechanisms that mediate fibrogenesis in patients with chronic intestinal inflammation. In the current review, we summarize recent evidence regarding the cellular and molecular factors of innate and adaptive immunity that are considered critical for the initiation and amplification of extracellular matrix deposition and stricture formation. We focus on the role of cytokines by dissecting the pro- vs antifibrotic components of the immune response, while taking into consideration their temporal association to the progressive stages of the natural history of IBD. We critically present evidence from animal models of intestinal fibrosis and analyze inflammation-fibrosis interactions that occur under such experimental scenarios. In addition, we comment on recent findings from large-scale, single-cell profiling of fibrosis-relevant populations in IBD patients. Based on such evidence, we propose future potential targets for antifibrotic therapies to treat patients with IBD.

Potential of Plant-sourced Phenols for Inflammatory Bowel Disease

2019 ◽  
Vol 25 (38) ◽  
pp. 5191-5217 ◽  
Author(s):  
Hai-tao Xiao ◽  
Bo Wen ◽  
Xiang-chun Shen ◽  
Zhao-xiang Bian
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Term Treatment ◽  
Term Therapy ◽  
Inflammatory Status ◽  
Long Term Treatment ◽  
Inflammatory Bowel ◽  
Chronic Intestinal Inflammation

Inflammatory bowel disease (IBD) is an uncontrolled chronic inflammatory intestinal disorder, which requires medications for long-term therapy. Facing the challenges of severe side effects and drug resistance of conventional medications, to develop the strategies meet the stringent safety and effectiveness in the long-term treatment are urgent in the clinics. In this regard, a growing body of evidence confirms plant-sourced phenols, such as flavonoids, catechins, stilbenes, coumarins, quinones, lignans, phenylethanoids, cannabinoid phenols, tannins, phenolic acids and hydroxyphenols, exert potent protective benefits with fewer undesirable effects in conditions of acute or chronic intestinal inflammation through improvement of colonic oxidative and pro-inflammatory status, preservation of the epithelial barrier function and modulation of gut microbiota. In this review, the great potential of plant-sourced phenols and their action mechanisms for the treatment or prevention of IBD in recent research are summarized, which may help further development of new preventive/adjuvant regimens for IBD.

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 A Rare Form of Chronic Granulomatous Disease (Type Iva) Presenting as Inflammatory Bowel Disease

1996 ◽  
Vol 10 (4) ◽  
pp. 221-224 ◽  
Author(s):  
Francisco A Sylvester
Keyword(s):  
Inflammatory Bowel Disease ◽  
Chronic Granulomatous Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Gastrointestinal Symptoms ◽  
Hypochromic Anemia ◽  
Granulomatous Disease ◽  
Poor Growth ◽  
Inflammatory Bowel ◽  
Chronic Intestinal Inflammation

Neutrophil dysfunction syndromes can sometimes mimic the clinical and pathological features of inflammatory bowel disease. The case of a 3.5-year-old boy with chronic diarrhea, abdominal pain, poor growth since infancy and microcytic, hypochromic anemia is presented. After an extensive diagnostic evaluation, he was found to have a rare variant (type IVA) of chronic granulomatous disease. His gastrointestinal symptoms markedly improved during therapy with gamma-interferon. Chronic granulomatous disease can present initially with a clinical picture suggestive of chronic intestinal inflammation. Therefore it should be considered in the differential diagnosis of atypical inflammatory bowel disease, both in children and young adults.

Lactobacillus paracasei L9 improves colitis by expanding butyrate-producing bacteria that inhibits the IL-6/STAT3 signaling pathway

2021 ◽  
Author(s):  
Zhengquan Yu ◽  
Min Deng ◽  
Xi Wu ◽  
Xiaoyue Duan ◽  
Jiuzhi Xu ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Signaling Pathway ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Lactobacillus Paracasei ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Inflammatory Bowel ◽  
Chronic Intestinal Inflammation

Inflammatory bowel disease (IBD) is a chronic intestinal inflammation that is currently incurable. Increasing evidences indicate that supplementation with probiotics could improve the symptoms of IBD. It is scientifically significant...

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 The Regulation of Intestinal Inflammation and Cancer Development by Type 2 Immune Responses

2020 ◽  
Vol 21 (24) ◽  
pp. 9772
Author(s):  
Reyes Gamez-Belmonte ◽  
Lena Erkert ◽  
Stefan Wirtz ◽  
Christoph Becker
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
Immune Responses ◽  
Immune Cells ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Clinical Care ◽  
Important Barrier ◽  
Inflammatory Bowel

The gut is among the most complex organs of the human body. It has to exert several functions including food and water absorption while setting up an efficient barrier to the outside world. Dysfunction of the gut can be life-threatening. Diseases of the gastrointestinal tract such as inflammatory bowel disease, infections, or colorectal cancer, therefore, pose substantial challenges to clinical care. The intestinal epithelium plays an important role in intestinal disease development. It not only establishes an important barrier against the gut lumen but also constantly signals information about the gut lumen and its composition to immune cells in the bowel wall. Such signaling across the epithelial barrier also occurs in the other direction. Intestinal epithelial cells respond to cytokines and other mediators of immune cells in the lamina propria and shape the microbial community within the gut by producing various antimicrobial peptides. Thus, the epithelium can be considered as an interpreter between the microbiota and the mucosal immune system, safeguarding and moderating communication to the benefit of the host. Type 2 immune responses play important roles in immune-epithelial communication. They contribute to gut tissue homeostasis and protect the host against infections with helminths. However, they are also involved in pathogenic pathways in inflammatory bowel disease and colorectal cancer. The current review provides an overview of current concepts regarding type 2 immune responses in intestinal physiology and pathophysiology.

scholarly journals Role of appendix in the development of inflammatory bowel disease in TCR-alpha mutant mice.

1996 ◽  
Vol 184 (2) ◽  
pp. 707-715 ◽  
Author(s):  
A Mizoguchi ◽  
E Mizoguchi ◽  
C Chiba ◽  
A K Bhan
Keyword(s):  
Inflammatory Bowel Disease ◽  
B Cells ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Embryonic Stem ◽  
Disease Process ◽  
Mutant Mice ◽  
Lymphoid Follicles ◽  
Inflammatory Bowel ◽  
Chronic Intestinal Inflammation

T cell receptor-alpha mutant mice (TCR-alpha-/-), created by gene targeting of the TCR-alpha gene in embryonic stem cells, spontaneously develop inflammatory bowel disease (IBD) resembling human ulcerative colitis. Since gut-associated lymphoid tissue is likely to play an important role in the development of chronic intestinal inflammation, we examined the changes in the appendix lymphoid follicle (ALF) and Peyer's patches (PP) in these mice. We found the structure of the ALF to be remarkably similar to that of the PP in the small intestine; in both instances, lymphoid follicles covered by surface epithelium (dome-formation) were found. The amount of proliferation in the lymphoid follicles of the appendix estimated by in vivo incorporation of 5-bromo-2'deoxyuridine was more than two times that of PP in TCR-alpha-/- mice. ELISPOT assay showed an increase of IgA, IgG1, and IgG2a, but not IgM-secreting B cells in ALF of TCR-alpha-/- mice compared to TCR-alpha+/- control mice. Furthermore, TCR-alpha-/- mice revealed an increase of autoantibody-producing B cells against the cytoskeletal protein tropomyosin in ALF as compared to PP. When TCR-alpha-/- mice underwent appendectomy at a young age (3-5 wk), the number of mesenteric lymph nodes cells at 6-7 mo were markedly less than in the sham-operated TCR-alpha-/- mice. Furthermore, appendectomy at 1 mo of age suppressed the development of IBD, with only 3.3% of these mice developing IBD in the 6-7-mo period of observation. In contrast, approximately 80% of controls, including the sham-operated TCR-alpha-/- mice, developed IBD during this period. These results suggest that ALF, rather than PP, is the priming site of cells involved in the disease process and plays an important role in the development of IBD in TCR-alpha-/- mice.

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