Adaptive immunity, chronic inflammation and the clock

Abstract

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.

The Role of Podoplanin in the Immune System and Inflammation

“…Inappropriate adaptive immune response can lead to development of autoimmune diseases, such as rheumatoid arthritis, psoriasis, and multiple sclerosis. 27 Furthermore, lymphangiogenesis is also associated with inflammation. The lymphatic system plays a crucial role in immune defense against infection by transporting immune cells from peripheral tissues to lymph nodes, especially in the rapid activation of adaptive immunity during inflammatory response.…”

Per1/Per2 knockout Affects Spleen Immune Function in Elderly Mice via Inducing Spleen Lymphocyte Ferroptosis

“…Disruption of the circadian rhythm can cause cardiovascular disease [ 4 ], gastrointestinal diseases [ 5 , 6 ], reproductive abnormalities [ 7 ], brain disorders [ 8 ], and immune system damage [ 9 , 10 ]. Recent work has found that cerebrospinal fluid (CSF) drains into the lymphatic system [ 11 ].…”

Role of Omega-3 Fatty Acids as Non-Photic Zeitgebers and Circadian Clock Synchronizers

“…Other components of the molecular clock, such as PER2 and REV-ERBα, showed oscillations in CD8+ T cells, as demonstrated through RNA sequencing [ 49 ]. The subset of T helper17 cells (Th17), which are involved in the defense against bacterial infections and the development of autoimmune diseases [ 50 ], changed in number according to the day/night cycle [ 51 ]. According to several studies in mice, REV-ERBα exerted negative feedback on Th17 cell development by influencing two transcription factors: RORγt, involved in Th17 differentiation [ 52 ]; and NFIL3, which downregulates RORγt [ 51 ].…”

“…According to several studies in mice, REV-ERBα exerted negative feedback on Th17 cell development by influencing two transcription factors: RORγt, involved in Th17 differentiation [ 52 ]; and NFIL3, which downregulates RORγt [ 51 ]. The maturation of dendritic cells, which constitute the antigen-presenting cells [ 50 ], was reported to be negatively regulated by REV-ERBα/β as well [ 53 ].…”