Type 2 immunity in intestinal homeostasis and inflammatory bowel disease

Immune Responses ◽

Bowel Disease ◽

Tissue Repair ◽

Lymphoid Cells ◽

Helminth Parasites ◽

Cellular Mechanisms ◽

Intestinal Homeostasis ◽

Type 2 immune responses commonly emerge during allergic reactions or infections with helminth parasites. Most of the cytokines associated with type 2 immune responses are IL-4, IL-5, and IL13, which are mainly produced by T helper 2 cells (TH2), eosinophils, basophils, mast cells, and group 2 innate lymphoid cells (ILC2s). Over the course of evolution, humans have developed type 2 immune responses to fight infections and to protect tissues from the potential collateral damage caused by inflammation. For example, worm parasites induce potent type 2 immune responses, which are needed to simultaneously clear the pathogen and to promote tissue repair following injury. Due to the strong type 2 immune responses induced by helminths, which can promote tissue repair in the damaged epithelium, their use has been suggested as a possible treatment for inflammatory bowel disease (IBD); however, the role of type 2 immune responses in the initiation and progression of IBD is not fully understood. In this review, we discuss the molecular and cellular mechanisms that regulate type 2 immune responses during intestinal homeostasis, and we briefly discuss the scarce evidence linking type 2 immune responses with the aetiology of IBD.

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

International Journal of Molecular Sciences ◽

10.3390/ijms21249772 ◽

2020 ◽

Vol 21 (24) ◽

pp. 9772

Author(s):

Reyes Gamez-Belmonte ◽

Lena Erkert ◽

Stefan Wirtz ◽

Christoph Becker

Keyword(s):

Colorectal Cancer ◽

Immune Responses ◽

Immune Cells ◽

Bowel Disease ◽

Intestinal Inflammation ◽

Clinical Care ◽

Important Barrier ◽

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.

Innate Lymphoid Cells in Intestinal Homeostasis and Inflammatory Bowel Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22147618 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7618

Author(s):

Angela Saez ◽

Raquel Gomez-Bris ◽

Beatriz Herrero-Fernandez ◽

Claudia Mingorance ◽

Cristina Rius ◽

...

Keyword(s):

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.

Nonhypoalbuminemic Inflammatory Bowel Disease in Dogs as Disease Model

Inflammatory Bowel Diseases ◽

10.1093/ibd/izab064 ◽

2021 ◽

Author(s):

Juan Hernandez ◽

Elodie Rouillé ◽

Florian Chocteau ◽

Marie Allard ◽

Karine Haurogné ◽

...

Keyword(s):

Immune Responses ◽

Bowel Disease ◽

Interindividual Variability ◽

Expression Patterns ◽

Disease Model ◽

Protein Loss ◽

Tissue Concentrations ◽

Inflammatory Bowel ◽

Antibody Levels

Abstract Background The incidence of inflammatory bowel disease (IBD) is increasing worldwide, emphasizing the need of relevant models, as dogs spontaneously affected by IBD may be, for better knowledge of the disease’s physiopathology. Methods We studied 22 client-owned dogs suffering from IBD without protein loss and 14 control dogs. Biopsies were obtained from the duodenum, ileum, and colon. Inflammatory grade was assessed by histopathology, immunohistochemistry, and chemokine analysis. The expression of Toll-like receptors (TLR) in mucosa was immunohistochemically evaluated. Antibody levels against bacterial ligands (lipopolysaccharide [LPS] and flagellin) were measured in sera using enzyme-linked immunoassay. Results Dogs with IBD showed low to severe clinical disease. Histopathologically, the gut of dogs with IBD did not exhibit significant alterations compared with controls except in the colon. The number of CD3+ T lymphocytes was decreased in the ileum and colon of dogs with IBD compared with controls, whereas the numbers of Foxp3+, CD20+, and CD204+ cells were similar in the 2 groups. Three chemokines, but no cytokines, were detected at the protein level in the mucosa, and the disease poorly affected their tissue concentrations. Dogs with IBD exhibited higher serum reactivity against LPS and flagellin than controls but similar immunoreactivity against the receptors TLR4 and TLR5. In addition, TLR2 and TLR9 showed similar expression patterns in both groups of dogs. Conclusions Our data described dysregulated immune responses in dogs affected by IBD without protein loss. Despite fairly homogeneous dog cohorts, we were still faced with interindividual variability, and new studies with larger cohorts are needed to validate the dog as a model.

Roles of Autophagy-Related Genes in the Pathogenesis of Inflammatory Bowel Disease

Cells ◽

10.3390/cells8010077 ◽

2019 ◽

Vol 8 (1) ◽

pp. 77 ◽

Cited By ~ 18

Author(s):

Sup Kim ◽

Hyuk Eun ◽

Eun-Kyeong Jo

Keyword(s):

Bowel Disease ◽

Intestinal Inflammation ◽

Paneth Cell ◽

Conditional Knockout ◽

Intestinal Homeostasis ◽

Genetic Studies ◽

Inflammatory Bowel ◽

Direct Targeting ◽

Catabolic Process

Autophagy is an intracellular catabolic process that is essential for a variety of cellular responses. Due to its role in the maintenance of biological homeostasis in conditions of stress, dysregulation or disruption of autophagy may be linked to human diseases such as inflammatory bowel disease (IBD). IBD is a complicated inflammatory colitis disorder; Crohn’s disease and ulcerative colitis are the principal types. Genetic studies have shown the clinical relevance of several autophagy-related genes (ATGs) in the pathogenesis of IBD. Additionally, recent studies using conditional knockout mice have led to a comprehensive understanding of ATGs that affect intestinal inflammation, Paneth cell abnormality and enteric pathogenic infection during colitis. In this review, we discuss the various ATGs involved in macroautophagy and selective autophagy, including ATG16L1, IRGM, LRRK2, ATG7, p62, optineurin and TFEB in the maintenance of intestinal homeostasis. Although advances have been made regarding the involvement of ATGs in maintaining intestinal homeostasis, determining the precise contribution of autophagy has remained elusive. Recent efforts based on direct targeting of ATGs and autophagy will further facilitate the development of new therapeutic opportunities for IBD.

Mo1900 – TNF-α Inhibitors and Risk of Type 2 Diabetes in Patients with Inflammatory Bowel Disease

Gastroenterology ◽

10.1016/s0016-5085(19)39167-x ◽

2019 ◽

Vol 156 (6) ◽

pp. S-879

Author(s):

Marie Villumsen ◽

Nynne Nyboe Andersen ◽

Tine Jess ◽

Kristine Allin

Keyword(s):

Type 2 Diabetes ◽

Bowel Disease ◽

Tnf Α ◽

A Comprehensive Review and Update on the Pathogenesis of Inflammatory Bowel Disease

Journal of Immunology Research ◽

10.1155/2019/7247238 ◽

2019 ◽

Vol 2019 ◽

pp. 1-16 ◽

Cited By ~ 35

Author(s):

Qingdong Guan

Keyword(s):

Immune Responses ◽

Bowel Disease ◽

Genetic Factors ◽

Intestinal Inflammation ◽

Adaptive Immune Responses ◽

Adaptive Immune ◽

Host Genetic ◽

Inflammatory Bowel ◽

Host Genetic Factors

Inflammatory bowel disease (IBD) is a chronic and life-threating inflammatory disease of gastroenteric tissue characterized by episodes of intestinal inflammation. The pathogenesis of IBD is complex. Recent studies have greatly improved our knowledge of the pathophysiology of IBD, leading to great advances in the treatment as well as diagnosis of IBD. In this review, we have systemically reviewed the pathogenesis of IBD and highlighted recent advances in host genetic factors, gut microbiota, and environmental factors and, especially, in abnormal innate and adaptive immune responses and their interactions, which may hold the keys to identify novel predictive or prognostic biomarkers and develop new therapies.

Metformin Use Is Associated with a Lower Risk of Inflammatory Bowel Disease in Patients with Type 2 Diabetes Mellitus

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjaa136 ◽

2020 ◽

Cited By ~ 1

Author(s):

Chin-Hsiao Tseng

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Bowel Disease ◽

Cox Regression ◽

Reference Group ◽

Hazard Ratios ◽

Abstract Aim Our aim was to compare the risk of developing inflammatory bowel disease [IBD] between ever users and never users of metformin. Methods Patients with newly diagnosed type 2 diabetes mellitus from 1999 to 2005 were enrolled from Taiwan’s National Health Insurance. A total of 340 211 ever users and 24 478 never users who were free from IBD on January 1, 2006 were followed up until December 31, 2011. Hazard ratios were estimated by Cox regression incorporating the inverse probability of treatment weighting using a propensity score. Results New-onset IBD was diagnosed in 6466 ever users and 750 never users. The respective incidence rates were 412.0 and 741.3 per 100 000 person-years and the hazard ratio for ever vs never users was 0.55 [95% confidence interval: 0.51–0.60]. A dose–response pattern was observed while comparing the tertiles of cumulative duration of metformin therapy to never users. The respective hazard ratios for the first [<26.0 months], second [26.0–58.3 months] and third [>58.3 months] tertiles were 1.00 [0.93–1.09], 0.57 [0.52–0.62] and 0.24 [0.22–0.26]. While patients treated with oral antidiabetic drugs [OADs] without metformin were treated as a reference group, the hazard ratios for patients treated with OADs with metformin, with insulin without metformin [with/without other OADs] and with insulin and metformin [with/without other OADs] were 0.52 [0.42–0.66], 0.95 [0.76–1.20] and 0.50 [0.40–0.62], respectively. Conclusion A reduced risk of IBD is consistently observed in patients with type 2 diabetes mellitus who have been treated with metformin.