Humoral Immunoregulation of Allergic Disease by Follicular T Cell Subsets

致病抗体促进和加重过敏性炎症。抗体反应由一种 T滤泡辅助细胞(TFH)的刺激信号和T细胞的抑制信号之间的微妙平衡 卵泡调节(TFR)细胞。这种平衡的改变可导致致病性抗体反应和 疾病。尽管Tfh和Tfr细胞亚群与控制过敏有关，但准确的 这些细胞如何调节不同阶段的过敏性炎症的机制目前尚不清楚。我们 假设TfH和TfR细胞的各个亚群在不同的阶段具有独特和多方面的作用 过敏性炎症。此外，我们假设TFH和TFR子集的组成在 是时候策划过敏性疾病了。通过阐明TFH和TFR细胞亚群是如何控制过敏性炎症的， 可以开发新的策略，专门针对过敏期间的致病反应，而不影响 广泛的免疫反应。为了验证这些假设，我们开发了一些新的小鼠模型 深入研究转铁蛋白和转铁蛋白受体细胞亚群在过敏中的作用。我们的目标是1) 确定TfR细胞如何通过调节B、Tfh13和Tfh21细胞来控制过敏性炎症；以及2)评估 独特的TFH细胞亚群的不断演变的组成如何协调过敏性炎症。我们的目标是 阐明Tfh和Tfr细胞亚群用于调节过敏的机制，并确定有针对性的策略 以限制过敏性炎症。

Pathogenic antibodies promote and exacerbate allergic inflammation. Antibody responses are controlled by a delicate balance between stimulatory signals from T follicular helper (Tfh) cells and inhibitory signals from T follicular regulatory (Tfr) cells. Alterations in this balance can lead to pathogenic antibody responses and disease. Although subsets of Tfh and Tfr cells have been implicated in controlling allergies, the precise mechanisms of how these cells regulate distinct stages of allergic inflammation are not currently known. We hypothesize that individual subsets of Tfh and Tfr cells have unique and multifaceted roles during distinct stages of allergic inflammation. Moreover, we hypothesize that the composition of Tfh and Tfr subsets evolves over time to orchestrate allergic disease. By elucidating how Tfh and Tfr cell subsets control allergic inflammation, new strategies can be developed that specifically target pathogenic responses during allergies without affecting broad immune responses. To test these hypotheses, we have developed a number of novel mouse models for the in-depth study of the roles of specialized subsets of Tfh and Tfr cells in allergies. Our aims are to 1) Determine how Tfr cells control allergic inflammation through regulating B, Tfh13 and Tfh21 cells; and 2) Assess how the evolving composition of unique Tfh cell subsets orchestrates allergic inflammation. Our goals are to elucidate mechanisms used by Tfh and Tfr cell subsets to regulate allergies, and to identify targeted strategies to limit allergic inflammation.