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Review
. 2025 Sep;13(9):e70246.
doi: 10.1002/iid3.70246.

Circadian Clock: A Regulator of Immunity in Autoimmune Diseases

Ye-Jun Wu  1 , Shu-Ying Zhang  1 , Hong-Yu Chen  1 , Xin-Ran He  1 , Guang-Rui Yang  1
Affiliations
Review

Circadian Clock: A Regulator of Immunity in Autoimmune Diseases

Ye-Jun Wu et al. Immun Inflamm Dis. 2025 Sep.

Abstract

Aim: Autoimmune diseases, characterized by the immune system mistakenly attacking the body's own tissues, are a growing global concern, with increasing prevalence. The circadian clock is a fundamental regulator of physiological processes, critically modulating immune functions. This review explores the intricate connections between circadian rhythms and immune responses in autoimmune pathogenesis and how disruptions exacerbate disease.

Methods: This synthesis examines recent research on circadian regulation of immune functions (leukocyte trafficking, cytokine secreion, phagocytosis) and autoimmune progression. Key evidence includes roles of core clock proteins such as brain and muscle ARNT-Like 1 (BMAL1), circadian locomotor output cycles kaput (CLOCK), and REV-ERBα, along with circadian-regulated immune cells, and impacts of environmental/lifestyle-induced circadian disruption.

Results: Ciradian rhythms significantly influence autoimmune disease progression and symptom patterns (e.g., morning joint stiffness in rheumatoid arthritis). Core clock proteins and rhythmic immune cells are critical for homeostasis. Circadian disruptions exacerbate immune dysfunction, promoting chronic inflammation and autoimmunity.

Conclusions: The circadian clock is a fundamental regulator of immune function and autoimmune pathogenesis. Disruption worsens disease progression. Understanding these mechanisms opens new avenues for therapeutic interventions, including chronotherapy and targeting clock genes, with the potential to improve treatment outcomes in autoimmune diseases.

Keywords: autoimmune diseases; circadian clock; immune system; rheumatoid arthritis; type 1 diabetes.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
The circadian regulation on the immune system. By Figdraw (www.figdraw.com).
See this image and copyright information in PMC

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