Amsterdam UMC, University of Amsterdam, Department of Experimental Immunology, Amsterdam Infection & Immunity Institute (AI&II), Cancer Center Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands.
Department of Pulmonary Medicine, Erasmus MC, Rotterdam, Netherlands.
Nat Commun. 2021 Oct 6;12(1):5841. doi: 10.1038/s41467-021-26187-x.
Phenotypic definition of helper ILC1 and NK cells is problematic due to overlapping markers. Recently we showed the identification of cytotoxic ILC3s characterized by expression of CD94. Here we analyse CD127+ ILCs and NK cells in intestinal lamina propria from healthy donors and Crohn's disease patients and identify two populations of CD127+CD94+ ILCs, designated population A and B, that can be distinguished on the expression of CD117, CD18 and cytotoxic molecules. Population B expresses granulysin, a cytotoxic molecule linked to bacterial lysis and/or chemotaxis of monocytes. Granulysin protein is secreted by population B cells upon stimulation with IL-15. Activation of population B in the presence of TGF-β strongly reduces the expression of cytotoxic effector molecules of population B. Strikingly, samples from individuals that suffer from active Crohn's disease display enhanced frequencies of granulysin-expressing effector CD127+CD94+ ILCs in comparison to controls. Thus this study identifies group 1 ILC populations which accumulate in inflamed intestinal tissue of Crohn's disease patients and may play a role in the pathology of the disease.
由于辅助性 ILC1 和 NK 细胞的表型定义存在重叠的标志物，因此其定义存在问题。最近，我们证明了可以通过表达 CD94 来鉴定细胞毒性 ILC3。在此，我们分析了来自健康供体和克罗恩病患者的肠道固有层中的 CD127+ILC 和 NK 细胞，并鉴定了两种 CD127+CD94+ILC 群体，分别命名为群体 A 和群体 B，它们可以通过表达 CD117、CD18 和细胞毒性分子来区分。群体 B 表达颗粒溶素，这是一种与细菌裂解和/或单核细胞趋化相关的细胞毒性分子。颗粒溶素蛋白可在 IL-15 刺激下由群体 B 细胞分泌。在 TGF-β 的存在下激活群体 B 会强烈降低群体 B 的细胞毒性效应分子的表达。引人注目的是，与对照组相比，患有活动性克罗恩病的个体样本中表达颗粒溶素的效应 CD127+CD94+ILC 的频率增加。因此，本研究鉴定了在克罗恩病患者炎症性肠道组织中积累的 ILC 群体 1，它们可能在疾病的发病机制中发挥作用。
