Human Microbiota Flagellins Drive Adaptive Immune Responses in Crohn's Disease.
Human Microbiota Flagellins Drive Adaptive Immune Responses in Crohn's Disease.
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DOI：
10.1053/j.gastro.2021.03.064
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发表时间：
2021-08
期刊：
影响因子：
29.4
通讯作者：
Elson CO
中科院分区：
文献类型：
--
作者：
Alexander KL;Zhao Q;Reif M;Rosenberg AF;Mannon PJ;Duck LW;Elson CO
克罗恩病和溃疡性结肠炎的特征在于遗传易感个体对微生物群的适应性免疫应答失调，但这些应答的特异性在很大程度上仍不确定。因此，我们开发了一种微生物群抗原微阵列来表征炎症性肠病中微生物抗体的反应性，特别是对人源性微生物群鞭毛蛋白的反应性。来自伯明翰的亚拉巴马大学的健康志愿者（n 87）和来自伯明翰医院的亚拉巴马大学的Kirklin诊所招募的患者（包括克罗恩病患者（n 152）和溃疡性结肠炎患者（n 170））的血清分别针对小鼠和人来源的微生物群细菌鞭毛蛋白进行探测，并分析IgG和伊加抗体应答。在选定的患者中分离并评价循环鞭毛蛋白反应性T效应细胞（CD4+CD154+）和T调节细胞（CD4+CD137+）。将获得的适应性免疫应答与相应的临床数据进行比较，以确定与疾病行为的相关性。我们发现IBD患者表达了对微生物群鞭毛蛋白的抗体反应性的选择性模式。克罗恩病患者，但不是溃疡性结肠炎患者，显示增强的血清IgG的人回肠本地化毛螺菌科鞭毛蛋白，与一个子集的患者具有高响应超过10鞭毛蛋白。对CBir1（一种临床上用于诊断CD的小鼠毛螺菌科鞭毛蛋白）的反应升高，与多毛螺菌科鞭毛蛋白反应性相关。在这一CD患者亚组中，多鞭毛蛋白反应性与鞭毛蛋白特异性CD154+CD45RA− T记忆细胞升高、鞭毛蛋白反应性CD4+ T调节细胞与T效应细胞比率降低以及疾病并发症发生率高相关。克罗恩病患者对人源性毛螺菌鞭毛蛋白表现出强烈的适应性免疫应答，这可能是预后和未来个性化治疗的目标。
Crohn’s disease and ulcerative colitis are characterized by dysregulated adaptive immune responses to the microbiota in genetically susceptible individuals, but the specificity of these responses remains largely undefined. Therefore, we developed a microbiota antigen microarray to characterize microbial antibody reactivity, particularly to human-derived microbiota flagellins, in inflammatory bowel disease. Sera from healthy volunteers (n 87) at the University of Alabama at Birmingham and from patients recruited from the Kirklin Clinic of University of Alabama at Birmingham Hospital, including patients with Crohn’s disease (n 152) and ulcerative colitis (n 170), were individually probed against microbiota bacterial flagellins of both mouse and human origin and analyzed for IgG and IgA antibody responses. Circulating flagellin-reactive T effector (CD4+CD154+) and T regulatory (CD4+CD137+) cells were isolated and evaluated in selected patients. Resulting adaptive immune responses were compared with corresponding clinical data to determine relevancy to disease behavior. We show that patients with IBD express selective patterns of antibody reactivity to microbiota flagellins. Patients with Crohn’s disease, but not patients with ulcerative colitis, display augmented serum IgG to human ileal-localized Lachnospiraceae flagellins, with a subset of patients having high responses to more than 10 flagellins. Elevated responses to CBir1, a mouse Lachnospiraceae flagellin used clinically to diagnose CD, correlated with multi-Lachnospiraceae flagellin reactivity. In this subset of patients with CD, multi-flagellin reactivity was associated with elevated flagellin-specific CD154+CD45RA− T memory cells, a reduced ratio of flagellin-reactive CD4+ T regulatory to T effector cells, and a high frequency of disease complications. Patients with Crohn’s disease display strong adaptive immune response to human-derived Lachnospiraceae flagellins, which may be targeted for prognosis and future personalized therapies.
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影响因子：
10.9
作者：
Hand, Timothy W.;Vujkovic-Cvijin, Ivan;Ridaura, Vanessa K.;Belkaid, Yasmine
通讯作者：
Belkaid, Yasmine
DOI：
10.1084/jem.20092253
发表时间：
2010-06-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Feng T;Wang L;Schoeb TR;Elson CO;Cong Y
通讯作者：
Cong Y
影响因子：
24.5
作者：
Canavan JB;Scottà C;Vossenkämper A;Goldberg R;Elder MJ;Shoval I;Marks E;Stolarczyk E;Lo JW;Powell N;Fazekasova H;Irving PM;Sanderson JD;Howard JK;Yagel S;Afzali B;MacDonald TT;Hernandez-Fuentes MP;Shpigel NY;Lombardi G;Lord GM
通讯作者：
Lord GM
影响因子：
14.2
作者：
Christmann, Benjamin S.;Abrahamsson, Thomas R.;Elson, Charles O.
通讯作者：
Elson, Charles O.
影响因子：
29.4
作者：
Landers, CJ;Cohavy, O;Targan, SR
通讯作者：
Targan, SR