Molecular Immunity Unit, Department of Medicine, University of Cambridge , Cambridge, UK.
NIHR Cambridge Biomedical Research Centre , Cambridge, UK.
Gut Microbes. 2020 Nov 9;12(1):1-9. doi: 10.1080/19490976.2019.1651596. Epub 2019 Sep 3.
Immunoglobulins (Igs) form a cornerstone of mucosal immunity. In the gastrointestinal tract, secretory IgA and IgM bind to commensal microorganisms within the intestinal lumen to prevent them from breaching the intestinal epithelium - a process known as immune exclusion. In recent years, there has been renewed interest in the role of IgG in intestinal immunity, driven in part by a genetic association of an affinity-lowering variant of an IgG receptor, FcγRIIA, with protection from ulcerative colitis (UC), a subclass of inflammatory bowel disease (IBD). We recently demonstrated a role for IgG and Fcγ receptor signalling in driving pathogenic IL-1β production by colonic mononuclear phagocytes and the subsequent induction of a local type 17 response in UC. Here, we discuss the potential relevance of our observations to the other major subclass of IBD - Crohn's disease (CD) - where the genetic association with variants is less robust and consider how this may impact therapeutic interventions in these disease subsets.
免疫球蛋白（Igs）是黏膜免疫的基石。在胃肠道中，分泌型 IgA 和 IgM 与肠腔中的共生微生物结合，防止它们穿透肠上皮——这一过程被称为免疫排斥。近年来，人们对 IgG 在肠道免疫中的作用重新产生了兴趣，部分原因是 IgG 受体 FcγRIIA 的亲和力降低的变异体与溃疡性结肠炎（UC）的保护作用有关，UC 是炎症性肠病（IBD）的一个亚类。我们最近证明了 IgG 和 Fcγ 受体信号在驱动结肠单核吞噬细胞产生致病性 IL-1β 以及随后在 UC 中诱导局部 17 型反应中的作用。在这里，我们讨论了我们的观察结果对另一种主要的 IBD 类别——克罗恩病（CD）的潜在相关性，在 CD 中，与变体的遗传关联不太稳健，并考虑这可能如何影响这些疾病亚类的治疗干预。
