ArticleClinical and experimental immunology2015
Regulation of the alternative pathway of complement modulates injury and immunity in a chronic model of dextran sulphate sodium-induced colitis.
Article in Clinical and experimental immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- The role of the complement system in gastrointestinal-related diseases.Frontiers in immunology · 2026Review
- The complement system in intestinal inflammation and cancer.The Journal of clinical investigation · 2025Review
- Enigmatic Roles of Complement Anaphylatoxin Signaling in Health and Disease.Immune network · 2025Review
- Proteomic profile of human colon organoids: effects of a multi-mineral intervention alone and in the presence of pro-inflammatory and anti-inflammatory treatments.Frontiers in gastroenterology (Lausanne, Switzerland) · 2025Article
- Body-wide genetic deficiency of poly(ADP-ribose) polymerase 14 sensitizes mice to colitis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Evidence for Genetic Causal Relationships Between Multiple Immune-Mediated Inflammatory Diseases and Age-Related Macular Degeneration: A Univariable and Multivariable Mendelian Randomization Study.Ophthalmology and therapy · 2024Article
- Milk-derived extracellular vesicles protect intestinal barrier integrity in the gut-liver axis.Science advances · 2023Article
- An Extremes of Phenotype Approach Confirms Significant Genetic Heterogeneity in Patients with Ulcerative Colitis.Journal of Crohn's & colitis · 2023Article
- Contribution of animal models to the mechanistic understanding of Alternative Pathway and Amplification Loop (AP/AL)-driven Complement-mediated Diseases.Immunological reviews · 2023Review
- Complement downregulation promotes an inflammatory signature that renders colorectal cancer susceptible to immunotherapy.Journal for immunotherapy of cancer · 2022Article
- Retinal drusen counts are increased in inflammatory bowel disease, and with longer disease duration, more complications and associated IgA glomerulonephritis.Scientific reports · 2022Observational
- Promotion of the inflammatory response in mid colon of complement component 3 knockout mice.Scientific reports · 2022Article
- Intestinal Fibrosis in Inflammatory Bowel Disease and the Prospects of Mesenchymal Stem Cell Therapy.Frontiers in immunology · 2022Review
- Upregulation of complement C1q reflects mucosal regeneration in a mouse model of colitis.Medical molecular morphology · 2021Article
- A Protective and Pathogenic Role for Complement During AcuteFrontiers in cellular and infection microbiology · 2021Review
- Deciphering microbiome and neuroactive immune gene interactions in schizophrenia.Neurobiology of disease · 2020Review
- Article
- Tissue-targeted complement therapeutics.Molecular immunology · 2018Review
- The alternative complement pathway is dysregulated in patients with chronic heart failure.Scientific reports · 2017Article
- A Targeted Inhibitor of the Alternative Complement Pathway Accelerates Recovery From Smoke-Induced Ocular Injury.Investigative ophthalmology & visual science · 2016Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The role of complement in inflammatory bowel disease (IBD) has been studied primarily using acute models, and it is unclear how complement affects processes in more relevant chronic models of IBD in which modulation of adaptive immunity and development of fibrosis have pathogenic roles. Using mice deficient in C1q/mannose-binding lectin (MBL) or C3, we demonstrated an important role for these opsonins and/or the classical pathway C3 convertase in providing protection against mucosal injury and infection in a model of chronic dextran sulphate sodium (DSS)-induced colitis. In contrast, deficiency of the alternative pathway (fB(-/-) mice) had significantly less impact on injury profiles. Consequently, the effect of a targeted inhibitor of the alternative pathway was investigated in a therapeutic protocol. Following the establishment of colitis, mice were treated with CR2-fH during subsequent periods of DSS treatment and acute injury (modelling relapse). CR2-fH significantly reduced complement activation, inflammation and injury in the colon, and additionally reduced fibrosis. Alternative pathway inhibition also altered the immune response in the chronic state in terms of reducing numbers of B cells, macrophages and mature dendritic cells in the lamina propria. This study indicates an important role for the alternative pathway of complement in the pathogenesis and the shaping of an immune response in chronic DSS-induced colitis, and supports further investigation into the use of targeted alternative pathway inhibition for the treatment of IBD.
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Registered trials
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