4.5 Review

Adaptive immunity, chronic inflammation and the clock

Journal

SEMINARS IN IMMUNOPATHOLOGY
Volume 44, Issue 2, Pages 209-224

Publisher

SPRINGER HEIDELBERG
DOI: 10.1007/s00281-022-00919-7

Keywords

Circadian; Adaptive immunity; Autoimmune disease; Lymphocyte

Funding

  1. Medical Research Council [22625]
  2. [MR/S002715/1]
  3. [MR/P023576/1]

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The adaptive immune system exhibits daily variation and is influenced by the circadian clock. The clock can regulate the function of the adaptive immune system through cell intrinsic mechanisms and cell extrinsic rhythmic signals. Disturbance of the circadian clock negatively impacts the development and progression of chronic inflammatory diseases.
The adaptive arm of the immune system facilitates recognition of specific foreign pathogens and, via the action of T and B lymphocytes, induces a fine-tuned response to target the pathogen and develop immunological memory. The functionality of the adaptive immune system exhibits daily 24-h variation both in homeostatic processes (such as lymphocyte trafficking and development of T lymphocyte subsets) and in responses to challenge. Here, we discuss how the circadian clock exerts influence over the function of the adaptive immune system, considering the roles of cell intrinsic clockwork machinery and cell extrinsic rhythmic signals. Inappropriate or misguided actions of the adaptive immune system can lead to development of autoimmune diseases such as rheumatoid arthritis, ulcerative colitis and multiple sclerosis. Growing evidence indicates that disturbance of the circadian clock has negative impact on development and progression of these chronic inflammatory diseases and we examine current understanding of clock-immune interactions in the setting of these inflammatory conditions. A greater appreciation of circadian control of adaptive immunity will facilitate further understanding of mechanisms driving daily variation in disease states and drive improvements in the diagnosis and treatment of chronic inflammatory diseases.

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