细胞生物学
生物
转录因子
信号转导
平衡
免疫学
生物化学
基因
作者
Yuning Lu,Gemma Basatemur,Ian Scott,Davide Chiarugi,Marc Clément,James Harrison,Ravin Jugdaohsingh,Lei Yu,Stephen A. Newland,Helen E. Jolin,Xuan Li,Xiao Chen,Monika Szymańska,Guttorm Haraldsen,Gaby Palmer,Padraic G. Fallon,E. Suzanne Cohen,Andrew N. J. McKenzie,Ziad Mallat
出处
期刊:Immunity
[Elsevier]
日期:2020-05-01
卷期号:52 (5): 782-793.e5
被引量:37
标识
DOI:10.1016/j.immuni.2020.03.006
摘要
Splenic red pulp macrophages (RPMs) contribute to erythrocyte homeostasis and are required for iron recycling. Heme induces the expression of SPIC transcription factor in monocyte-derived macrophages and promotes their differentiation into RPM precursors, pre-RPMs. However, the requirements for differentiation into mature RPMs remain unknown. Here, we have demonstrated that interleukin (IL)-33 associated with erythrocytes and co-cooperated with heme to promote the generation of mature RPMs through activation of the MyD88 adaptor protein and ERK1/2 kinases downstream of the IL-33 receptor, IL1RL1. IL-33- and IL1RL1-deficient mice showed defective iron recycling and increased splenic iron deposition. Gene expression and chromatin accessibility studies revealed a role for GATA transcription factors downstream of IL-33 signaling during the development of pre-RPMs that retained full potential to differentiate into RPMs. Thus, IL-33 instructs the development of RPMs as a response to physiological erythrocyte damage with important implications to iron recycling and iron homeostasis.
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