Bouteau Aurélie, Qin Zhen, Zurawski Sandra, Zurawski Gerard, Igyártó Botond Z
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107, United States.
Baylor Scott & White Research Institute, Dallas, TX 75204, United States.
bioRxiv. 2025 Feb 19:2025.01.10.632426. doi: 10.1101/2025.01.10.632426.
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 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引导辅助性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和系统，研究了稳态LC诱导的适应性免疫反应的潜在机制。我们发现，LCs驱动生发中心Tfh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，而这些信号传导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。我们的研究结果挑战了传统的三信号范式，证明了在稳态下，细胞因子信号传导对于LC介导的Tfh和B细胞反应是可有可无的。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发展自身免疫中的作用提供了一个框架。
