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Interleukin-33 Signaling Controls the Development of Iron-Recycling Macrophages

Published inImmunity
Publication date2020
Abstract

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.

Citation (ISO format)
LU, Yuning et al. Interleukin-33 Signaling Controls the Development of Iron-Recycling Macrophages. In: Immunity, 2020. doi: 10.1016/j.immuni.2020.03.006
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ISSN of the journal1074-7613
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Creation04/17/2020 1:11:00 PM
First validation04/17/2020 1:11:00 PM
Update time03/15/2023 9:50:22 PM
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