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A recent study has identified a distinct subset of γδ T cells, termed GD3 cells, which produce IL-3 and play a crucial role in modulating sensory neurons' sensitivity to allergens. This interaction forms the foundation of a novel γδ T cell–IL-3 axis, which has been shown to be instrumental in initiating allergic responses, particularly allergic pruritus (itching).
The study utilized various allergic models, including allergens such as papain and dust mites, to demonstrate that IL-3 acts through its receptor on sensory neurons, lowering their activation threshold and making them more susceptible to allergic triggers. This pathway is upstream of allergic inflammation, indicating that IL-3 not only amplifies sensory responses but also contributes to the broader immune activation observed in chronic allergic conditions. Importantly, the researchers found that blocking this pathway in mouse models significantly reduced allergic pruritus, highlighting IL-3 as a potential therapeutic target for conditions such as atopic dermatitis.
Moreover, the study reveals that this process is independent of traditional immune mediators like mast cells and eosinophils, commonly implicated in allergic responses, underscoring the unique role of GD3 cells and the IL-3 axis in sensory neuron modulation. These findings provide critical insights into the neuro-immune interface, demonstrating how immune cells can directly influence neural circuits involved in allergic disease.
This discovery suggests that targeted inhibition of IL-3 signaling could offer new therapeutic strategies for managing chronic allergic diseases by disrupting the neuro-immune feedback loop that exacerbates symptoms. Additionally, the study contributes to the broader understanding of how immune cells interact with the nervous system, providing a foundation for future investigations into allergic disease pathogenesis and treatment development.
DOI: 10.1126/sciimmunol.ado0398
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The research primarily focuses on how effector regulatory T cells (eTregs) respond to HRD and PARP inhibitor (PARPi) therapies, which are widely used in treating HRD-positive tumors. Key findings indicate that eTregs, which typically suppress immune responses, are highly responsive in HRD environments. Their presence often correlates with the accumulation of other immune cells, particularly terminally exhausted CD8+ T cells (Tex). Interestingly, chronic interferon signaling in HRD tumors upregulates immune checkpoints, influencing both Treg and Tex pathways. In this context, the study suggests that depleting eTregs combination with PARP inhibitors or chemotherapy could significantly suppress tumor growth in HRD-positive cancers. The research used both single-cell gene expression and T cell receptor profiling from over 100 HGSOC samples to understand how HRD and related therapies affect the tumor microenvironment (TME). The results showed that neoadjuvant PARPi monotherapy (e.g., niraparib) achieved high response rates, making eTregs a promising therapeutic target. The study also demonstrated that targeting eTregs, either through direct depletion or via therapies like anti-CCR8 in mouse models, can reduce tumor progression without noticeable toxicity, suggesting potential therapeutic applications beyond ovarian cancer. This research underscores the importance of understanding the interplay between tumor-intrinsic genetic defects like HRD and the immune microenvironment, paving the way for new approaches to immunotherapy in HRD-related cancers.
DOI: 10.1016/j.cell.2024.06.013
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Editor & Reviewer: Yanwen Zhu
