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SP0193 Physiologic Functions of Innate Immunity in Metabolic Homeostasis
  1. A. Chawla
  1. Cardiovascular Research Institute, Departments of Physiology and Medicine, University of California San Francisco, San Francisco, CA, United States

Abstract

Macrophages take residence in nearly all tissues, where they function as sensors and integrators of environmental and metabolic stress. In metabolic tissues, tissue resident macrophages sense their local and systemic environment to coordinate parenchymal cell metabolism. In this context, previous work from our laboratory has focused on the transcriptional regulation of the inducible program of alternative macrophage activation, and its importance in adaptations to dietary and environmental stress. In addition to the homeostatic functions of inducible macrophage activation, we postulated that innate immune responses might be regulated in an anticipatory manner, allowing organisms to anticipate and adapt to changes in their environment. Here, we present evidence that Ly6Chi inflammatory monocytes exhibit diurnal variation, which controls their trafficking to sites of inflammation. This cyclic pattern of trafficking confers protection against Listeria monocytogenes and is regulated by the repressive activity of the circadian gene BMAL1. Accordingly, myeloid cell-specific deletion of BMAL1 induces expression of monocyte-attracting chemokines and disrupts rhythmic cycling of Ly6Chi monocytes, predisposing mice to development of pathologies associated with acute and chronic inflammation. These findings have unveiled a critical role for BMAL1 in controlling the diurnal rhythms in Ly6Chi monocytes that enhances organismal fitness.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.6271

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