Ronchese Franca, Webb Greta R, Ochiai Sotaro, Lamiable Olivier, Brewerton Maia
Malaghan Institute of Medical Research, Wellington, New Zealand.
Department of Clinical Immunology and Allergy, Auckland City Hospital, Auckland, New Zealand.
Allergy. 2025 Feb;80(2):395-407. doi: 10.1111/all.16337. Epub 2024 Sep 26.
Allergic disease is caused by the activation of allergen-specific CD4+ type-2 T follicular helper cells (Tfh2) and T helper 2 (Th2) effector cells that secrete the cytokines IL-4, IL-5, IL-9, and IL-13 upon allergen encounter, thereby inducing IgE production by B cells and tissue inflammation. While it is accepted that the priming and differentiation of naïve CD4+ T cells into Th2 requires allergen presentation by type 2 dendritic cells (DC2s), the underlying signals remain unidentified. In this review we focus on the interaction between allergen-presenting DC2s and naïve CD4+ T cells in lymph node (LN), and the potential mechanisms by which DC2s might instruct Th2 differentiation. We outline recent advances in characterizing DC2 development and heterogeneity. We review mechanisms of allergen sensing and current proposed mechanisms of Th2 differentiation, with specific consideration of the role of DC2s and how they might contribute to each mechanism. Finally, we assess recent publications reporting a detailed analysis of DC-T cell interactions in LNs and how they support Th2 differentiation. Together, these studies are starting to shape our understanding of this key initial step of the allergic immune response.
过敏性疾病是由过敏原特异性CD4+ 2型滤泡辅助性T细胞（Tfh2）和辅助性T细胞2（Th2）效应细胞的激活所引起的，这些细胞在接触过敏原时会分泌细胞因子白细胞介素-4（IL-4）、白细胞介素-5（IL-5）、白细胞介素-9（IL-9）和白细胞介素-13，从而诱导B细胞产生免疫球蛋白E（IgE）并引发组织炎症。虽然人们普遍认为，初始CD4+ T细胞向Th2细胞的致敏和分化需要2型树突状细胞（DC2s）呈递过敏原，但其潜在信号仍未明确。在这篇综述中，我们重点关注淋巴结（LN）中呈递过敏原的DC2s与初始CD4+ T细胞之间的相互作用，以及DC2s指导Th2细胞分化的潜在机制。我们概述了在DC2发育和异质性特征研究方面的最新进展。我们回顾了过敏原感知机制以及当前提出的Th2细胞分化机制，特别考虑了DC2s的作用以及它们如何对每种机制产生影响。最后，我们评估了最近发表的关于详细分析淋巴结中DC-T细胞相互作用以及它们如何支持Th2细胞分化的文献。总之，这些研究开始塑造我们对过敏性免疫反应这一关键初始步骤的理解。
