# Circadian dysregulation of immune function in SLE

> **NIH NIH R21** · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · 2020 · $197,158

## Abstract

ABSTRACT
Circadian rhythm is a universal phenomenon that allows organisms to anticipate and respond to
changes in their environment by regulating sleep and feeding patterns, blood pressure,
metabolism, detoxification and response to pathogens. Disruption of circadian rhythm
contributes to multiple human diseases including cardiovascular diseases, cancer, depression,
kidney diseases, metabolic syndrome and inflammation. In previous studies, we found that there
is dampening of the renal circadian clock in mouse models of lupus with significant effects on
renal physiology including cell metabolism, ion and water transport and blood pressure control.
Recent studies have shown that immune function is also tightly regulated by the circadian clock,
particularly in monocytes and macrophages. Diurnal variation in inflammatory monocyte release
from the bone marrow has a major influence on immune responses to infectious organisms as
well as inflammatory responses to tissue damage. Macrophages also have heightened immune
surveillance capabilities during the awake hours when exposure to environmental challenges is
more likely to occur. Inflammation dampens circadian rhythms leading to a constant state of
heightened immune awareness and amplification of the inflammatory state. This new proposal
will focus on the role of the monocyte/macrophage circadian clock in mouse models of lupus.
Most studies so far have focused on acute infectious and inflammatory conditions that
temporarily suppress circadian regulators and there is little known about the effect of chronic
inflammatory states on circadian functions in macrophages. Our first aim will address the
hypothesis that disruption of the circadian clock in macrophages leads to amplification of
inflammatory processes in lupus. We will examine the circadian regulation of peripheral blood
monocytes and spleen macrophages and the effect of chronic lupus inflammation on both gene
expression patterns and macrophage functions over time during the 24 hour circadian period.
Our second aim will address the hypothesis that BMAL1 is a major regulator of macrophage
circadian rhythm that protects from inflammation and enhances renal repair. Here we will use
mice with macrophage-specific BMAL1 deletion to examine the role of BMAL1 in both spleen
and renal macrophages in a lupus model. These studies could lead to new approaches that
involve normalization of the macrophage clock so as to help restore immune tolerance.

## Key facts

- **NIH application ID:** 9874708
- **Project number:** 1R21AR076557-01
- **Recipient organization:** FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
- **Principal Investigator:** Anne Davidson
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $197,158
- **Award type:** 1
- **Project period:** 2020-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9874708

## Citation

> US National Institutes of Health, RePORTER application 9874708, Circadian dysregulation of immune function in SLE (1R21AR076557-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9874708. Licensed CC0.

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