Dupré Loïc, Castanon Irinka, Boztug Kaan
Toulouse Institute for Infectious and Inflammatory Diseases (INFINITy), INSERM, CNRS, Toulouse University, Toulouse, France.
Medical University of Vienna, Department of Dermatology, Vienna, Austria.
Nat Rev Immunol. 2025 Sep 10. doi: 10.1038/s41577-025-01214-w.
Actin cytoskeleton remodelling drives the migration of immune cells and their engagement in dynamic cell-cell contacts. The importance of actin cytoskeleton dynamics in immune cell function is highlighted by the discovery of inborn errors of immunity (IEIs) that are caused by defects in individual actin-regulatory proteins, resulting in immune-related actinopathies. In addition to susceptibility to infection, these often present with a vast array of autoimmune and autoinflammatory manifestations. Here, we review the role of actin subnetworks in the activation and function of lymphoid and myeloid cells. We focus on the mechanisms by which actin defects result in aberrant lymphocyte function, including dysregulation of T cell- and B cell-mediated tolerance and biased cytokine production, which can result in autoimmunity. We also highlight the relationship between actin defects and inflammasome activation and other pathomechanisms in myeloid cells as the underlying cause of autoinflammation. Finally, we discuss future avenues for research and therapeutic intervention based on a molecular understanding of immune-related actinopathies.
肌动蛋白细胞骨架重塑驱动免疫细胞迁移及其参与动态细胞间接触。免疫相关肌动蛋白病是由个别肌动蛋白调节蛋白缺陷引起的先天性免疫缺陷（IEIs），这凸显了肌动蛋白细胞骨架动力学在免疫细胞功能中的重要性。除了易感染外，这些疾病还常常伴有大量自身免疫和自身炎症表现。在这里，我们综述肌动蛋白亚网络在淋巴细胞和髓细胞激活及功能中的作用。我们重点关注肌动蛋白缺陷导致淋巴细胞功能异常的机制，包括T细胞和B细胞介导的耐受性失调以及细胞因子产生偏向，这可能导致自身免疫。我们还强调肌动蛋白缺陷与髓细胞中炎性小体激活及其他病理机制之间的关系，这是自身炎症的潜在原因。最后，我们基于对免疫相关肌动蛋白病的分子理解，讨论未来的研究途径和治疗干预措施。
