生理微生物暴露短暂抑制小鼠肺ILC2对过敏原的反应

SCI 11 December 2022

Physiological microbial exposure transiently inhibits mouse lung ILC2 responses to allergens

(Nature Immunology, IF: 31.250)

Katharine E. Block, Koji Iijima, Mark J. Pierson, Daniel A. Walsh, Rinna Tei, Tamara A. Kucaba, Julie X5, Mohammad Haneef Khan, Christopher Staley, Thomas S. Griffith, Henry J. McSorley, Hirohito Kita & Stephen C. Jameson

CORRESPONDENCE TO: kita.hirohito@mayp.edu, james024@umn.edu 

Objectives 目的  

Lung group 2 innate lymphoid cells (ILC2s) control the nature of immune responses to airway allergens. Some microbial products, including those that stimulate interferons, block ILC2 activation, but whether this occurs after natural infections or causes durable ILC2 inhibition is unclear. In the present study, we cohoused laboratory and pet store mice as a model of physiological microbial exposure. Laboratory mice cohoused for 2 weeks had impaired ILC2 responses and reduced lung eosinophilia to intranasal allergens, whereas these responses were restored in mice cohoused for ≥2 months. ILC2 inhibition at 2 weeks correlated with increased interferon receptor signaling, which waned by 2 months of cohousing. Reinduction of interferons in 2-month cohoused mice blocked ILC2 activation. These findings suggest that ILC2s respond dynamically to environmental cues and that microbial exposures do not control long-term desensitization of innate type 2 responses to allergens.

肺2型固有淋巴细胞（ILC2）控制对气道过敏原的免疫反应的性质。一些微生物产物，包括那些刺激干扰素的微生物产物，可以阻断ILC2的激活，但目前尚不清楚这是发生在自然感染后还是微生物产物导致持久的ILC2抑制。在本研究中，我们将实验室小鼠和宠物店小鼠共同饲养作为微生物暴露生理反应的模型。实验室小鼠在共同饲养2周后，ILC2反应受损，针对鼻内过敏原的肺嗜酸性粒细胞减少，而这些反应在小鼠在暴露≥2个月后恢复。2周时的ILC2抑制与增加的干扰素受体信号传导相关，其通过2个月的暴露而减弱。在2个月的同组小鼠中干扰素的再产生阻断了ILC2的激活。这些发现表明ILC2对环境线索有动态反应，微生物暴露不能控制先天性2型过敏反应的长期脱敏。

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