Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany.
Institute for Infectious Diseases and Zoonoses, University of Munich LMU, 80539 Munich, Germany.
Cell Rep. 2018 Apr 17;23(3):783-795. doi: 10.1016/j.celrep.2018.03.072.
The processes underlying the development and maintenance of tertiary lymphoid organs are incompletely understood. Using a Ccr7 knockout/knockin approach, we show that spontaneous bronchus-associated lymphoid tissue (BALT) formation can be caused by CCR7-mediated migration defects of dendritic cells (DCs) in the lung. Plt/plt mice that lack the CCR7 ligands CCL19 and CCL21-serine do not form BALT spontaneously because lung-expressed CCL21-leucine presumably suffices to maintain steady-state DC egress. However, plt/plt mice are highly susceptible to modified vaccinia virus infection, showing enhanced recruitment of immune cells as well as alterations in CCR7-ligand-mediated lymphocyte egress from the lungs, leading to dramatically enhanced BALT. Furthermore, we identify two independent BALT homing routes for blood-derived lymphocytes. One is HEV mediated and depends on CCR7 and L-selectin, while the second route is via the lung parenchyma and is independent of these molecules. Together, these data provide insights into CCR7/CCR7-ligand-orchestrated aspects in BALT formation.
三级淋巴器官发育和维持的潜在机制尚未完全阐明。我们使用 Ccr7 敲除/敲入方法表明，肺部树突状细胞（DC）的 CCR7 介导的迁移缺陷可导致自发性支气管相关淋巴组织（BALT）的形成。缺乏 CCR7 配体 CCL19 和 CCL21-丝氨酸的 Plt/plt 小鼠不会自发形成 BALT，因为肺部表达的 CCL21-亮氨酸可能足以维持稳态 DC 迁出。然而，plt/plt 小鼠对改良痘苗病毒感染高度敏感，表现出免疫细胞的强烈募集以及 CCR7 配体介导的淋巴细胞从肺部迁出的改变，导致 BALT 显著增强。此外，我们鉴定了两种用于血液来源淋巴细胞的独立 BALT 归巢途径。一种是通过 HEV 介导的，依赖于 CCR7 和 L-选择素，而第二种途径是通过肺实质，不依赖于这些分子。这些数据共同提供了对 BALT 形成中 CCR7/CCR7 配体协调方面的深入了解。
