簇状细胞IL-17RB抑制IL-25的生物利用度，揭示了环境依赖性ILC2的低增殖，这一成果由苏黎世大学Christoph Schneider团队经过不懈努力而取得。相关论文发表在2025年3月12日出版的《自然—免疫学》杂志上。

簇状细胞- 2组先天淋巴样细胞（ILC2）回路在检测微生物来源的琥珀酸和管腔蠕虫时协调快速的2型反应。他们的发现描绘了涉及IP3R2接合和Ca²⁺通量的关键机制步骤，控制由琥珀酸检测触发的簇状细胞产生的白细胞介素-25 （IL-25）。虽然IL-17RB在ILC2激活中具有关键的内在作用，但它在簇状细胞中发挥调节功能。簇状细胞表现出组成性Il25表达，使它们处于预期状态，促进IL-25蛋白的快速产生，从而激活ILC2。簇状细胞IL-17RB对于抑制IL-25的生物利用度，防止Il25基础表达引起的过度补性ILC2刺激至关重要。簇状细胞Il17rb缺乏或长时间琥珀酸暴露导致IL-25对ILC2的超优化刺激可诱导ILC2s的低增殖状态，这在慢性蠕虫感染中也观察到。他们的研究为IL-25在这一回路中的调控动力学提供了重要的见解，强调了对不同腔态的反应所需的微妙调节。

附：英文原文

Title: Tuft cell IL-17RB restrains IL-25 bioavailability and reveals context-dependent ILC2 hypoproliferation

Author: Feng, Xiaogang, Andersson, Tilde, Flchter, Pascal, Gschwend, Julia, Berest, Ivan, Muff, Julian L., Lechner, Antonie, Gondrand, Aurelia, Westermann, Patrick, Brander, Nina, Carchidi, Daniele, De Tenorio, Jeshua C., Pan, Tianlang, Boehm, Ulrich, Klose, Christoph S. N., Artis, David, Messner, Christoph B., Leinders-Zufall, Trese, Zufall, Frank, Schneider, Christoph

Issue&Volume: 2025-03-12

Abstract: The tuft cell–group 2 innate lymphoid cell (ILC2) circuit orchestrates rapid type 2 responses upon detecting microbially derived succinate and luminal helminths. Our findings delineate key mechanistic steps involving IP3R2 engagement and Ca2+ flux, governing interleukin-25 (IL-25) production by tuft cells triggered by succinate detection. While IL-17RB has a pivotal intrinsic role in ILC2 activation, it exerts a regulatory function in tuft cells. Tuft cells exhibit constitutive Il25 expression, placing them in an anticipatory state that facilitates rapid production of IL-25 protein for ILC2 activation. Tuft cell IL-17RB is crucial for restraining IL-25 bioavailability, preventing excessive tonic ILC2 stimulation due to basal Il25 expression. Supraoptimal ILC2 stimulation by IL-25 resulting from tuft cell Il17rb deficiency or prolonged succinate exposure induces a state of hypoproliferation in ILC2s, also observed in chronic helminth infection. Our study offers critical insights into the regulatory dynamics of IL-25 in this circuit, highlighting the delicate tuning required for responses to diverse luminal states.

DOI: 10.1038/s41590-025-02104-y

Source: https://www.nature.com/articles/s41590-025-02104-y