美国西奈山伊坎医学院Saurabh Mehandru研究小组研究发现溃疡性结肠炎(UC)的特征是与疾病活动相关的浆母细胞会干扰体液免疫。相关论文于2022年2月21日发表在《自然-医学》杂志上。
在这项研究中，研究人员招募了三组UC患者（主要队列，n=145；验证队列1，n=664；验证队列2，n=143），以全面确定UC相关肠道炎症患者中B细胞的分布。使用单细胞RNA测序、单细胞IgH基因测序和蛋白质水平验证，研究人员绘制了粘膜和循环B细胞的组成、转录和克隆型图谱。研究人员在黏膜B细胞室内发现了主要的差异，包括初始B细胞和IgG+浆细胞的扩增，其多样性和成熟度降低。
此外，研究人员在炎症UC患者肠道中分离出靶向整合素αvβ6的自身反应性浆细胞克隆。研究还鉴定了一个与致病性B细胞反应相关的肠道表达CXCL13的TFH样外周辅助性T细胞子集。最后，在所有三个队列中，研究证实肠道体液免疫的变化反映在循环系统中与疾病活动相关肠道归巢浆母细胞的扩增，这可以预测疾病进展。该数据表明UC中存在高度失调的B细胞反应，并突出了B细胞在疾病发病过程中的潜在作用。
据了解，B细胞对肠道稳态至关重要但其在UC中的研究稀缺。
附：英文原文
Title: Ulcerative colitis is characterized by a plasmablast-skewed humoral response associated with disease activity
Author: Uzzan, Mathieu, Martin, Jerome C., Mesin, Luka, Livanos, Alexandra E., Castro-Dopico, Tomas, Huang, Ruiqi, Petralia, Francesca, Magri, Giuliana, Kumar, Shashi, Zhao, Qing, Rosenstein, Adam K., Tokuyama, Minami, Sharma, Keshav, Ungaro, Ryan, Kosoy, Roman, Jha, Divya, Fischer, Jeremy, Singh, Harpriya, Keir, Mary E., Ramamoorthi, Nandhini, Gorman, William E. O, Cohen, Benjamin L., Rahman, Adeeb, Cossarini, Francesca, Seki, Akihiro, Leyre, Louise, Vaquero, Sonia Tejedor, Gurunathan, Sakteesh, Grasset, Emilie K., Losic, Bojan, Dubinsky, Marla, Greenstein, Alexander J., Gottlieb, Zoe, Legnani, Peter, George, James, Irizar, Haritz, Stojmirovic, Aleksandar, Brodmerkel, Carrie, Kasarkis, Andrew, Sands, Bruce E., Furtado, Glaucia, Lira, Sergio A., Tuong, Zewen K., Ko, Huaibin M., Cerutti, Andrea, Elson, Charles O., Clatworthy, Menna R., Merad, Miriam, Surez-Farias, Mayte, Argmann, Carmen, Hackney, Jason A., Victora, Gabriel D., Randolph, Gwendalyn J., Kenigsberg, Ephraim, Colombel, Jean Frederic, Mehandru, Saurabh
Issue&Volume: 2022-02-21
Abstract: B cells, which are critical for intestinal homeostasis, remain understudied in ulcerative colitis (UC). In this study, we recruited three cohorts of patients with UC (primary cohort, n=145; validation cohort 1, n=664; and validation cohort 2, n=143) to comprehensively define the landscape of B cells during UC-associated intestinal inflammation. Using single-cell RNA sequencing, single-cell IgH gene sequencing and protein-level validation, we mapped the compositional, transcriptional and clonotypic landscape of mucosal and circulating B cells. We found major perturbations within the mucosal B cell compartment, including an expansion of naive B cells and IgG+ plasma cells with curtailed diversity and maturation. Furthermore, we isolated an auto-reactive plasma cell clone targeting integrin αvβ6 from inflamed UC intestines. We also identified a subset of intestinal CXCL13-expressing TFH-like T peripheral helper cells that were associated with the pathogenic B cell response. Finally, across all three cohorts, we confirmed that changes in intestinal humoral immunity are reflected in circulation by the expansion of gut-homing plasmablasts that correlates with disease activity and predicts disease complications. Our data demonstrate a highly dysregulated B cell response in UC and highlight a potential role of B cells in disease pathogenesis.
DOI: 10.1038/s41591-022-01680-y
Source: https://www.nature.com/articles/s41591-022-01680-y
Nature Medicine：《自然—医学》，创刊于1995年。隶属于施普林格·自然出版集团，最新IF：87.241
官方网址：https://www.nature.com/nm/
投稿链接：https://mts-nmed.nature.com/cgi-bin/main.plex
本期文章：《自然—医学》：Online/在线发表
