Sleep influences the immune response and the rejection process alters sleep pattern: Evidence from a skin allograft model in mice

Sleep influences the immune response and the rejection process alters sleep pattern: Evidence from a skin allograft model in mice

Author Ruiz, Francieli Silva Autor UNIFESP Google Scholar
Andersen, Monica Levy Autor UNIFESP Google Scholar
Guindalini, Camila Autor UNIFESP Google Scholar
Araujo, Leandro Pires Autor UNIFESP Google Scholar
Lopes, Jose Daniel Autor UNIFESP Google Scholar
Tufik, Sergio Autor UNIFESP Google Scholar
Abstract Introduction: Sleep generally regulates immune functions in a supportive manner and can affect parameters that are directly involved in the rejection process. Study objectives: The first objective was to assess whether sleep deprivation (SD) or sleep restriction (SR) affects the allograft rejection process in mice. The second objective was to investigate whether the rejection process itself modulates the sleep pattern of allografted mice. Design: Adult BALB/c and C57BL/6J male mice were used as the donors and recipients, respectively, except for the syngeneic group (ISOTX), which received skin from mice of the same strain (C57BL/6J). The recipients were randomly assigned to either one of two control groups - TX (allogenic) or ISOTX (syngeneic) - which underwent stereotaxic surgery to enable sleep recording prior to the allograft but were not sleep deprived

one of two paradoxical sleep deprived groups - SDTX and TXSD - which underwent 72 h of continuous SD either before or after the allograft respectively, and one of two sleep restricted groups - SRTX and TXSR - which underwent 21 h of SD and 3 h of sleep for 15 days either before or after the allograft respectively. Interventions: The skin allograft was inspected daily to determine the survival time, expected as 8.0 +/- 0.4 days in this transplant model under no treatment. The sleep pattern was controlled throughout the rejection process in the SD and SR groups. Draining lymph nodes, spleen, blood and skin grafts were harvested on the 5th day after transplantation for evaluation of the immune parameters related to allograft rejection. Measurements and results: In the control groups, we observed a reduction in paradoxical sleep throughout the entire allograft rejection process. Acute and chronic experimental sleep loss in the SD and SR groups produced marked alterations in the immune response. Both SD and SR prolonged allograft survival compared to the non-sleep-deprived group. There were reductions in the following parameters involved in the allograft rejection under sleep loss: CD4(+) and CD8(+) T cell subpopulations in the peripheral lymph organs and spleen, circulating sIL-2R levels, graft-infiltrating CD4(+) T cells and skin allograft global gene expression. Conclusions: We provide, as far as we are aware, the first evidence in vivo that the immune response can alter the normal sleep pattern, and that sleep loss can conversely affect the immune response related to graft rejection. (C) 2017 Elsevier Inc. All rights reserved.
Keywords Sleep
Sleep deprivation
Immune system
T cells
Gene expression
xmlui.dri2xhtml.METS-1.0.item-coverage San Diego
Language English
Sponsor Associacao Fundo de Incentivo a Pesquisa (AFIP)
Grant number FAPESP: 98/14303-3
FAPESP: 07/55445-6
Date 2017
Published in Brain Behavior And Immunity. San Diego, v. 61, p. 274-288, 2017.
ISSN 0889-1591 (Sherpa/Romeo, impact factor)
Publisher Academic Press Inc Elsevier Science
Extent 274-288
Access rights Closed access
Type Article
Web of Science ID WOS:000395365900030

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