Chair of Pharmacology, Department of Medicine, Faculty of Science, University of Fribourg, Fribourg, Switzerland.
School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland.
Eur J Immunol. 2021 Aug;51(8):1980-1991. doi: 10.1002/eji.202049120. Epub 2021 Jun 16.
High mobility group box-1 protein (HMGB1) is an alarmin that, once released, promotes inflammatory responses, alone and as a complex with the chemokine CXCL12. Here, we report that the HMGB1-CXCL12 complex plays an essential role also in homeostasis by controlling the migration of B lymphocytes. We show that extracellular HMGB1 is critical for the CXCL12-dependent egress of B cells from the Peyer's patches (PP). This promigratory function of the complex was restricted to the PPs, since HMGB1 was not required for B-cell migratory processes in other locations. Accordingly, we detected higher constitutive levels of the HMGB1-CXCL12 complex in PPs than in other lymphoid organs. HMGB1-CXCL12 in vivo inhibition was associated with a reduced basal IgA production in the gut. Collectively, our results demonstrate a role for the HMGB1-CXCL12 complex in orchestrating B-cell trafficking in homeostasis, and provide a novel target to control lymphocyte migration in mucosal immunity.
高迁移率族蛋白 B1（HMGB1）是一种警报素，一旦释放，就会单独或与趋化因子 CXCL12 形成复合物，促进炎症反应。在这里，我们报告 HMGB1-CXCL12 复合物通过控制 B 淋巴细胞的迁移，在维持体内平衡方面也起着至关重要的作用。我们表明，细胞外 HMGB1 对于 B 细胞从派尔氏集合淋巴结（PP）中依赖 CXCL12 的迁出是至关重要的。该复合物的促迁移功能仅限于 PP，因为 HMGB1 对于其他部位的 B 细胞迁移过程并不必需。因此，我们在 PP 中检测到比其他淋巴器官更高的 HMGB1-CXCL12 复合物的组成性水平。体内抑制 HMGB1-CXCL12 与肠道中基础 IgA 产生减少有关。总的来说，我们的结果表明 HMGB1-CXCL12 复合物在协调体内平衡中的 B 细胞迁移中起作用，并为控制粘膜免疫中淋巴细胞迁移提供了一个新的靶点。
