Bouteau Aurélie, Qin Zhen, Zurawski Sandra, Zurawski Gerard, Igyártó Botond Z
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA, United States.
Baylor Scott and White Research Institute, Dallas, TX, United States.
Front Immunol. 2025 Jul 18;16:1611812. doi: 10.3389/fimmu.2025.1611812. eCollection 2025.
Dendritic cells (DCs) are key regulators of adaptive immunity, guiding T helper (Th) cell differentiation through antigen presentation, co-stimulation, and cytokine production. However, in steady-state conditions, certain DC subsets, such as Langerhans cells (LCs), induce T follicular helper (Tfh) cells and B cell responses without inflammatory stimuli. Using multiple mouse models and systems, we investigated the mechanisms underlying steady-state LC-induced adaptive immune responses. We found that LCs drive germinal center Tfh and B cell differentiation and antibody production independently of interleukin-6 (IL-6), type-I interferons, and ICOS ligand (ICOS-L) signaling, which are critical in inflammatory settings. Instead, these responses relied on CD80/CD86-mediated co-stimulation. Our findings challenge the conventional three-signal paradigm by demonstrating that canonical cytokine signaling is dispensable for LC-mediated Tfh and B cell responses in steady-state. These insights provide a framework for understanding homeostatic immunity and the immune system's role in maintaining tolerance or developing autoimmunity under non-inflammatory conditions.
树突状细胞（DCs）是适应性免疫的关键调节因子，通过抗原呈递、共刺激和细胞因子产生来指导辅助性T（Th）细胞分化。然而，在稳态条件下，某些DC亚群，如朗格汉斯细胞（LCs），在没有炎症刺激的情况下诱导滤泡辅助性T（Tfh）细胞和B细胞反应。我们使用多种小鼠模型及系统，研究了稳态LC诱导适应性免疫反应的潜在机制。我们发现，LCs驱动生发中心Tfh细胞和B细胞分化以及抗体产生，这一过程不依赖于白细胞介素-6（IL-6）、I型干扰素和可诱导共刺激分子配体（ICOS-L）信号传导，而这些在炎症环境中至关重要。相反，这些反应依赖于CD80/CD86介导的共刺激。我们的研究结果通过证明在稳态下，经典细胞因子信号传导对于LC介导的Tfh细胞和B细胞反应并非必需，从而挑战了传统的三信号范式。这些见解为理解稳态免疫以及免疫系统在非炎症条件下维持耐受性或引发自身免疫中的作用提供了一个框架。
