微生物学和免疫学分部Arash Grakoui课题组近日取得一项新成果。经过不懈努力，他们报道了iHALT开启了肝脏作为替代次要淋巴器官的功能。相关论文于2025年11月26日发表在《自然》杂志上。

在这里，研究人员证明了典型的系统性病毒感染确实诱导了SLO中产生的肝脏转运浆细胞，而严格的嗜肝性肝炎病毒感染则在肝脏中诱导了局部启动的、病毒特异性的浆细胞，而与SLO的贡献无关。这种局部衍生的后代来自可诱导的肝相关淋巴组织（iHALT）结构，其中包含T滤泡辅助细胞、髓细胞和生发中心样B细胞的生殖病灶，通常来自单个门静脉周围结构特有的单个创始克隆，并支持局部体细胞超突变。关键的是，小鼠中这种iHALT结构的细胞组成、细胞-细胞接触伙伴和微结构与人类肝炎病毒感染密切相关。功能上依赖于CD40L信号传导和同源B细胞受体特异性，新出现的CXCR4⁺VLA-4⁺LFA-1⁺CD44⁺CD138⁺浆细胞立即沿CXCL12⁺纤维连接蛋白⁺ICAM2⁺骨桥蛋白⁺I型胶原⁺门脉周围成纤维束保留，作为同源锚定对其维持至关重要。总之，研究组描述了在SLO休眠期间，体液免疫完全在肝脏病毒感染的淋巴外部位产生和维持，其中功能性iHALT成功地补偿了严格的嗜肝病毒诱导的SLO逃避策略，以防止持续感染。

据悉，在病毒感染后，目前的体液免疫模式假设发生在次级淋巴器官（SLO）内的生发中心反应产生效应浆细胞，这些效应浆细胞随后运输到受感染的器官或骨髓。然而，目前尚不清楚病毒组织趋向性如何控制这种反应的时空动态。

附：英文原文

Title: iHALT unlocks liver functionality as a surrogate secondary lymphoid organ

Author: Gridley, John, Pak, David, Kumari, Anuradha, Shupak, Jacob, Holland, Brantley, Shi, Yifeng, Trivedi, Sheetal, Wang, Yongtao, Kasturi, Sudhir Pai, Kapoor, Amit, Chung, Raymond T., Grakoui, Arash

Issue&Volume: 2025-11-26

Abstract: Upon viral infection, the current paradigm of humoral immunity posits that germinal centre reactions occurring within secondary lymphoid organs (SLOs) yield effector plasma cells that subsequently traffic to infected organs or the bone marrow1,2,3. However, it is not well understood how viral tissue tropism may govern the spatiotemporal dynamics of such responses. Here we demonstrate that infection with a prototypical systemic virus indeed induces liver-trafficking plasma cells generated in SLOs, whereas strictly hepatotropic hepaciviral infection elicits locally primed, virus-specific plasma cells in the liver independently of SLO contribution. Such locally derived progenies emerged from inducible hepatic-associated lymphoid tissue (iHALT) structures containing generative foci of T follicular helper cells, myeloid cells and germinal centre-like B cells, often arising from single founder clones unique to individual periportal structures and locally supporting somatic hypermutation. Critically, the cellular composition, cell–cell contact partners and microarchitecture of such iHALT structures in mice were closely mirrored upon hepaciviral infection in humans. Functionally dependent upon CD40L signalling and cognate B cell receptor specificity, emerging CXCR4+VLA-4+LFA-1+CD44+CD138+ plasma cells were immediately retained along CXCL12+fibronectin+ICAM2+osteopontin+type I collagen+ periportal fibroblast tracts, acting as cognate anchoring pairs that were critical to their maintenance therein. In summary, we characterize humoral immunity exclusively generated and maintained within its extralymphoid site of viral infection in the liver amidst SLO dormancy, in which functional iHALT successfully compensates for strictly hepatotropic virus-induced SLO-evasion strategies to prevent persistent infection.

DOI: 10.1038/s41586-025-09803-4

Source: https://www.nature.com/articles/s41586-025-09803-4