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Mechanisms associated with flares and remission in colitis

结肠炎发作和缓解的相关机制

基本信息

批准号：
10623214
负责人：
SERGIO A. LIRA
金额：
$ 73.42万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-05-01 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10623214
关键词：
Affect Animals Antigens Autoimmune Diseases Bacteria Beverages Binding Biology CD4 Positive T Lymphocytes Candy Cecum Cells Chemicals Cherry - dietary Child Citrobacter rodentium Clinical Colitis Colon Consumption Cosmetics Coupled Dairying Data Dendritic Cells Developing Countries Development Diet Diet Habits Disease Disease remission Environmental Risk Factor Etiology Exposure to Flare Food Food Coloring Agents Generations Genes Genetic Genetic study Haptens Hormones Human Hydration status Immune Immune response Immune system In Vitro Incidence Incubated Individual Infection Inflammatory Inflammatory Bowel Diseases Injections Intestines Life Link Medicine Modern Medicine Mus Myeloid Cells Naphthols Pharmaceutical Preparations Prevention Production Property Proteins Regulatory T-Lymphocyte Research Project Grants Role Signal Pathway T-Lymphocyte Testing Tissues Wild Type Mouse Work cytokine dietary experimental study gut inflammation interest interleukin-23 microbiota response soft drink

项目摘要

Summary Inflammatory bowel diseases (IBD) affect millions of individuals worldwide and its incidence is increasing. Both genetic and environmental factors appear to play a role in IBD development. Genetic studies in humans have linked the interleukin-23 (IL-23) signaling pathway with IBD, but the environmental factors contributing to disease, have remained elusive. The rising incidence of worldwide IBD has been associated with westernization of dietary habits in developing countries, however there is little scientific evidence to support causality. In this application we will examine the role of a particular group of dietary additives, namely food colorants, to development of colitis. We have now discovered that the food colorant Red 40, also known as Allura Red AC, promotes colitis in mice that conditionally express low levels of IL-23 (referred to as R23FR mice), but not in wild type mice. Red 40 is the most abundant food colorant in the world, with annual production exceeding 2.3 million kg. It is widely used in as red colorant in soft drinks, cherry flavored products, candy, dairy, drugs, and cosmetics. Of interest, the Red 40-containing beverages, Kool-Aid and the hydrating solution Pedialyte Cherry can also cause colitis in R23FR mice. Red 40-induced colitis in R23FR mice requires the microbiota and CD4+ T cells. Based on these and other results presented here, we formulate a central hypothesis that the Red 40 or its metabolites haptenize bacterial or endogenous proteins to generate tolerance in wild type mice, or colitis in mice in which IL-23 expression is dysregulated. We will study in this proposal the mechanisms involved in generation and prevention of these responses. Specifically, we will define: 1) if Red 40 and its metabolite ANSA are haptens; 2) how Red 40 induces tolerance in control mice; and 3) if Red 40 or ANSA-specific T cells are generated in R23FR mice

总结

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

CCR8 marks highly suppressive Treg cells within tumours but is dispensable for their accumulation and suppressive function.

DOI：
10.1111/imm.13337
发表时间：
2021-08
期刊：
Immunology
影响因子：
6.4
作者：
Whiteside SK;Grant FM;Gyori DS;Conti AG;Imianowski CJ;Kuo P;Nasrallah R;Sadiyah F;Lira SA;Tacke F;Eil RL;Burton OT;Dooley J;Liston A;Okkenhaug K;Yang J;Roychoudhuri R
通讯作者：
Roychoudhuri R

Interleukin 1 beta and Matrix Metallopeptidase 3 Contribute to Development of Epidermal Growth Factor Receptor-Dependent Serrated Polyps in Mouse Cecum.

白细胞介素 1 β 和基质金属肽酶 3 有助于小鼠盲肠中表皮生长因子受体依赖性锯齿状息肉的形成。

DOI：
10.1053/j.gastro.2019.08.025
发表时间：
2019
期刊：
Gastroenterology
影响因子：
29.4
作者：
He,Zhengxiang;Chen,Lili;Chen,Grace;Smaldini,Paola;Bongers,Gerold;Catalan-Dibene,Jovani;Furtado,GlauciaC;Lira,SergioA
通讯作者：
Lira,SergioA

Interleukin 33 regulates gene expression in intestinal epithelial cells independently of its nuclear localization.

DOI：
10.1016/j.cyto.2018.08.009
发表时间：
2018-11
期刊：
Cytokine
影响因子：
3.8
作者：
He Z;Chen L;Furtado GC;Lira SA
通讯作者：
Lira SA

Food colorants metabolized by commensal bacteria promote colitis in mice with dysregulated expression of interleukin-23.

DOI：
10.1016/j.cmet.2021.04.015
发表时间：
2021-07-06
期刊：
Cell metabolism
影响因子：
29
作者：
He Z;Chen L;Catalan-Dibene J;Bongers G;Faith JJ;Suebsuwong C;DeVita RJ;Shen Z;Fox JG;Lafaille JJ;Furtado GC;Lira SA
通讯作者：
Lira SA

Host and microbiota interactions are critical for development of murine Crohn's-like ileitis.