Brain, behavior, and immunity · 2025
Temporally-regulated genetic access to IL-1β-expressing cellular networks in homeostasis and following peripheral or central immune stimuli.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Nemeth Daniel P, Liu Xiaoyu, Chen Loretta, Hawkins Margaret R, Ali Haroon S, Lapid Madison G, Farsian Vesal, Kim Ashley, Saez Julianna, Maxey Gabriella, Luqman Numana, McGovern Samantha, Schrier Matt, Vargas Chris, Juste-Ellis Josh St, Yip Jasmine, Romain Joris, Bachstetter Adam D, Quan Ning
Аннотация
BACKGROUND: The proinflammatory cytokine Interleukin-1 beta (IL-1β) regulates nearly all aspects of immune function. In the brain, IL-1β is implicated in neural and immune functions under both basal and inflammatory conditions. Under basal conditions, IL-1β is known to alter sleep, memory, and affect. Under inflammatory conditions, IL-1β can induce sickness behaviors, HPA activation, and exacerbate neurological and psychological disorders. Sensitive detection and specific manipulation of IL-1β-expressing cells in the brain is currently not achievable; therefore, we generated the first mouse line to allow both robust visualization and genetic manipulation of the IL-1β-expressing cells.
METHODS: The IL-1β-TRAP mouse was generated through Crispr9-mediated recombination. IRES-CreERT2 was inserted following exon 7 after the stop codon of the Il1b gene which yielded an IL-1β-IRES-Cre-ERT2 mouse (IL-1β-TRAP). To visualize IL-1β-expressing cells, IL-1β-IRES-Cre-ERT2 line was crossed with ROSA26-lox-stop-lox-tdTomato mouse to generate the IL-1β-IRES-Cre-ERT2:ROSA26-lox-stop-lox-tdTomato (IL-1β-TRAP-reporter). The IL-1β-TRAP-reporter mice were given intraperitoneal (i.p.) Tamoxifen before peripheral LPS or central IL-1β administration. PBS was used as control. The IL-1β-TRAP-reporter mice were also exposed to repetitive closed head injury (CHI) or i.p. kainic acid. tdTomato was allowed to express for 7d and distribution of IL-1β-expressing cells were observed via immunohistochemistry and/or lightsheet microscopy.
RESULTS: Under basal conditions, IL-1β was found primarily to be expressed in MHCII+ and CD206+ meningeal and ventricular macrophages with sparse IL-1β-expressing microglia and neurons in brain parenchyma. Following i.p. LPS and i.c.v. IL-1β injections, IL-1β expression was found in meningeal macrophages and parenchymal P2YR12+ microglia. Following CHI, IL-1β-expressing macrophages increased in the meninges and IL-1β-expressing microglia were induced in the parenchyma at the injury site and along white matter tracts.
CONCLUSIONS: This is the first time active populations of cytokine-expressing cells are visualized, characterized, and genetically accessed using a mouse line with a knockin CreER. With this tool, we identified the choroid plexus as the predominant IL-1β-expressing region in homeostasis. Further, this mouse can be used to identify newly activated IL-1β-expressing cells; they can be targeted for manipulation in physiological and pathological contexts.
METHODS: The IL-1β-TRAP mouse was generated through Crispr9-mediated recombination. IRES-CreERT2 was inserted following exon 7 after the stop codon of the Il1b gene which yielded an IL-1β-IRES-Cre-ERT2 mouse (IL-1β-TRAP). To visualize IL-1β-expressing cells, IL-1β-IRES-Cre-ERT2 line was crossed with ROSA26-lox-stop-lox-tdTomato mouse to generate the IL-1β-IRES-Cre-ERT2:ROSA26-lox-stop-lox-tdTomato (IL-1β-TRAP-reporter). The IL-1β-TRAP-reporter mice were given intraperitoneal (i.p.) Tamoxifen before peripheral LPS or central IL-1β administration. PBS was used as control. The IL-1β-TRAP-reporter mice were also exposed to repetitive closed head injury (CHI) or i.p. kainic acid. tdTomato was allowed to express for 7d and distribution of IL-1β-expressing cells were observed via immunohistochemistry and/or lightsheet microscopy.
RESULTS: Under basal conditions, IL-1β was found primarily to be expressed in MHCII+ and CD206+ meningeal and ventricular macrophages with sparse IL-1β-expressing microglia and neurons in brain parenchyma. Following i.p. LPS and i.c.v. IL-1β injections, IL-1β expression was found in meningeal macrophages and parenchymal P2YR12+ microglia. Following CHI, IL-1β-expressing macrophages increased in the meninges and IL-1β-expressing microglia were induced in the parenchyma at the injury site and along white matter tracts.
CONCLUSIONS: This is the first time active populations of cytokine-expressing cells are visualized, characterized, and genetically accessed using a mouse line with a knockin CreER. With this tool, we identified the choroid plexus as the predominant IL-1β-expressing region in homeostasis. Further, this mouse can be used to identify newly activated IL-1β-expressing cells; they can be targeted for manipulation in physiological and pathological contexts.