Intestinal Immunity in health and disease

健康和疾病中的肠道免疫

• 批准号: MC_UU_00036/1
• 负责人: Alison Simmons
• 金额: $ 309.63万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Intramural
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MC_UU_00036%2F1
• 关键词: Intestinal; Immunity; health; disease

The intestine is a major immune organ, housing up to 70% of the body’s immune cells and incorporating a luminal surface area of about 32 square meters. The intestine must balance its role in absorption of nutrients with optimal immune function. The intestinal immune system must co-exists symbiotically with luminal microbes whilst eliminating harmful pathogens to prevent these from entering the blood and lymph circulatory systems. Disturbance in intestinal immunity contributes to a variety of conditions including inflammatory bowel disease (IBD), cancer and aging. IBD affects several million people world-wide and up to 40% patients fail to respond to available, largely generic immunosuppressant medication. In IBD intestinal immunity is dysregulated leading to destruction of normal intestinal cellular physiology and function. We develop or optimise state of the art technologies and apply these to define molecular pathways governing human intestinal immune health and IBD. We take advantage of our large clinical cohorts to directly map human intestinal pathology in all sub forms of the disease including patients with complex drug resistant complications. This information is used to inform design of novel therapeutics to improve management of this condition. Our work contributes to the broader aim of the MRC Translational Immune Discovery Unit to define human tissue and barrier immunology and its dysregulation in a variety of immune mediated inflammatory disorders.

肠道是主要的免疫器官，容纳高达70%的身体免疫细胞，并包含约32平方米的管腔表面积。肠道必须平衡其吸收营养的作用与最佳的免疫功能。肠道免疫系统必须与肠道微生物共生共存，同时消除有害病原体，以防止这些病原体进入血液和淋巴循环系统。肠道免疫功能紊乱导致多种疾病，包括炎症性肠病（IBD）、癌症和衰老。IBD影响全球数百万人，高达40%的患者对可用的，主要是通用的免疫抑制剂药物没有反应。在IBD中，肠道免疫失调，导致正常肠道细胞生理和功能的破坏。我们开发或优化最先进的技术，并应用这些技术来定义管理人类肠道免疫健康和IBD的分子途径。我们利用我们的大型临床队列直接映射人类肠道病理学的所有亚型的疾病，包括复杂的耐药并发症的患者。这些信息用于设计新的治疗方法，以改善对这种疾病的管理。我们的工作有助于MRC转化免疫发现部门的更广泛目标，即定义人体组织和屏障免疫学及其在各种免疫介导的炎症性疾病中的失调。

项目成果

HLA-DP on Epithelial Cells Enables Tissue Damage by NKp44+ Natural Killer Cells in Ulcerative Colitis.

上皮细胞上的 HLA-DP 可导致溃疡性结肠炎中 NKp44 自然杀伤细胞造成组织损伤。

• DOI: 10.1053/j.gastro.2023.06.034
• 发表时间: 2023
• 期刊: Gastroenterology
• 影响因子: 29.4
• 作者: Baumdick,MartinE;Niehrs,Annika;Degenhardt,Frauke;Schwerk,Maria;Hinrichs,Ole;Jordan-Paiz,Ana;Padoan,Benedetta;Wegner,LucyHM;Schloer,Sebastian;Zecher,BrittaF;Malsy,Jakob;Joshi,VinitaR;Illig,Christin;Schröder-Schwarz,Jennifer

Anti-TNF Biologicals Enhance the Anti-Inflammatory Properties of IgG N-Glycome in Crohn's Disease.

• DOI: 10.3390/biom13060954
• 发表时间: 2023-06-07
• 期刊: Biomolecules
• 影响因子: 5.5

GSDMB is increased in IBD and regulates epithelial restitution/repair independent of pyroptosis.

IBD中的GSDMB增加，并调节上皮恢复/修复，而与凋亡无关。

• DOI: 10.1016/j.cell.2021.12.024
• 发表时间: 2022-01-20
• 期刊: Cell
• 影响因子: 64.5
• 作者: Rana N;Privitera G;Kondolf HC;Bulek K;Lechuga S;De Salvo C;Corridoni D;Antanaviciute A;Maywald RL;Hurtado AM;Zhao J;Huang EH;Li X;Chan ER;Simmons A;Bamias G;Abbott DW;Heaney JD;Ivanov AI;Pizarro TT
• 通讯作者: Pizarro TT

A systems approach evaluating the impact of SARS-CoV-2 variant of concern mutations on CD8+ T cell responses.

• DOI: 10.1093/immadv/ltad005
• 发表时间: 2023
• 期刊: Immunotherapy advances

A Roadmap for the Human Gut Cell Atlas.

• DOI: 10.1038/s41575-023-00784-1
• 发表时间: 2023-09
• 期刊: Nature reviews. Gastroenterology & hepatology