Affiliation:
1. WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan
2. Department of Orthopedic Surgery, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
3. Yokohama City Minato Red Cross Hospital, Kanagawa 231-8682, Japan
Abstract
Various aspects of the immune system display circadian rhythms. Although lymphocyte trafficking has been suggested to show diurnal variations, the mechanisms and influences on immune responses are unclear. Here, we show in mice that inputs from adrenergic nerves contribute to the diurnal variation of lymphocyte recirculation through lymph nodes (LNs), which is reflected in the magnitude of the adaptive immune response. Neural inputs to β2-adrenergic receptors (β2ARs) expressed on lymphocytes reduced the frequency of lymphocyte egress from LNs at night, which was accompanied by an increase of lymphocyte numbers in LNs. Immunization during the period of lymphocyte accumulation in LNs enhanced antibody responses. The diurnal variation of the humoral immune response was dependent on β2AR-mediated neural signals and was diminished when lymphocyte recirculation through LNs was stopped. This study reveals the physiological role of adrenergic control of lymphocyte trafficking in adaptive immunity and establishes a novel mechanism that generates diurnal rhythmicity in the immune system.
Funder
Japan Society for the Promotion of Science
Ministry of Education, Culture, Sports, Science and Technology
Japan Medical Association
Uehara Memorial Foundation
Naito Foundation
Takeda Science Foundation
Astellas Foundation for Research on Metabolic Disorders
Mochida Memorial Foundation for Medical and Pharmaceutical Research
Publisher
Rockefeller University Press
Subject
Immunology,Immunology and Allergy
Cited by
139 articles.
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