Department of Immunology and Regenerative Biology, Weizmann Institute of Science, Rehovot, Israel.
Department of Cell Biology, Faculty of Science, Charles University, Prague, Czech Republic.
Nat Rev Immunol. 2024 Jan;24(1):64-77. doi: 10.1038/s41577-023-00906-5. Epub 2023 Jul 21.
Antigen-presenting cells (APCs) are master regulators of the immune response by directly interacting with T cells to orchestrate distinct functional outcomes. Several types of professional APC exist, including conventional dendritic cells, B cells and macrophages, and numerous other cell types have non-classical roles in antigen presentation, such as thymic epithelial cells, endothelial cells and granulocytes. Accumulating evidence indicates the presence of a new family of APCs marked by the lineage-specifying transcription factor retinoic acid receptor-related orphan receptor-γt (RORγt) and demonstrates that these APCs have key roles in shaping immunity, inflammation and tolerance, particularly in the context of host-microorganism interactions. These RORγt APCs include subsets of group 3 innate lymphoid cells, extrathymic autoimmune regulator-expressing cells and, potentially, other emerging populations. Here, we summarize the major findings that led to the discovery of these RORγt APCs and their associated functions. We discuss discordance in recent reports and identify gaps in our knowledge in this burgeoning field, which has tremendous potential to advance our understanding of fundamental immune concepts.
抗原提呈细胞(APCs)通过直接与 T 细胞相互作用来协调不同的功能结果,是免疫反应的主要调节者。几种类型的专业 APC 存在,包括传统的树突状细胞、B 细胞和巨噬细胞,许多其他细胞类型在抗原提呈中具有非经典作用,如胸腺上皮细胞、内皮细胞和粒细胞。越来越多的证据表明存在一类新的 APC,其特征是由谱系特异性转录因子维甲酸受体相关孤儿受体-γt(RORγt)标记,并证明这些 APC 在塑造免疫、炎症和耐受方面具有关键作用,特别是在宿主-微生物相互作用的情况下。这些 RORγt APC 包括 3 组先天淋巴细胞的亚群、表达外胸腺自身免疫调节因子的细胞,以及可能的其他新兴群体。在这里,我们总结了导致这些 RORγt APC 及其相关功能发现的主要发现。我们讨论了最近报告中的不一致之处,并确定了这一新兴领域知识中的差距,这为我们深入了解基本免疫概念提供了巨大的潜力。