Invariant Natural Killer T cells resilience to paradoxical sleep deprivation-associated stress

Author(s)

Sousa, Maria E. P. ^[1] ; Gonzatti, Michelangelo B. ^[1] ; Fernandes, Edgar R. ^[1] ; Freire, Beatriz M. ^[1] ; Guereschi, Marcia G. ^[1] ; Basso, Alexandre S. ^[1] ; Andersen, Monica L. ^[2] ; Rosa, Daniela S. ^{[3, 1]} ; Keller, Alexandre C. ^[1]

Affiliation

^[1] Fed Univ Sao Paulo UNIFESP EPM, Dept Microbiol Immunol & Parasitol, Rua Botucatu, 4th Floor, BR-04023062 Sao Paulo - Brazil

^[2] Fed Univ Sao Paulo UNIFESP EPM, Dept Psychobiol, Rua Botucatu, 862, 1st Floor, BR-04023062 Sao Paulo - Brazil

^[3] Inst Invest Immunol Iii INCT, Sao Paulo - Brazil

• Document type: Journal article
• Source: BRAIN BEHAVIOR AND IMMUNITY; v. 90, p. 208-215, NOV 2020.
• Web of Science Citations: 0

Abstract

Although several studies demonstrate that stressful situations, such as sleep disturbances, negatively impact the innate and adaptive arms of the immune system, their influence on invariant Natural Killer T (iNKT) cells remains unclear. iNKT cells are CD1d-restricted innate T cells that recognize glycolipid antigens and rapidly produce polarizing cytokines being key players in several immune responses, and a potential target for immunotherapy. iNKT cells differ in several aspects from conventional T lymphocytes, including a unique dependence on CD1d-expressing double-positive (DP) thymocytes for intrathymic maturation. As a consequence of stress, DP thymocytes undergo glucocorticoid-induced apoptosis, which might compromise iNKT developmental pathway. Therefore, we used a paradoxical sleep deprivation (SD) model to determine the impact of sleep disturbance on iNKT cell biology. After 72 h of SD, C57Bl/6 mice exhibited a significant increase in systemic glucocorticoid levels and thymus atrophy. Despite marked decrease in the number of DP thymocytes, the ratio CD1d(+)/CD1d(-) was higher in SD mice, and the number of thymic iNKT cells remained unaltered, suggesting that SD did not compromise the iNKT developmental pathway. In contrast, SD reduced hepatic IFN-gamma, but not, IL-4-producing iNKT cells, without further effect in the spleen. Despite this fact, SD did not affect stimulation of IFN-gamma production by iNKT cells, or cytokine release, in response to alpha-galactosylceramide, a specific antigen. Furthermore, although SD impaired splenic NK cells activity against tumor cells, it did not affect iNKT cell-specific cytotoxicity. Thus, our study shows that SD-induced stress did not impair the iNKT cells' responses to a cognate antigen. (AU)

• FAPESP's process: 17/17471-7 - Antigenicity and immunogenicity of Zika virus envelope recombinant proteins
• Grantee: Daniela Santoro Rosa
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/11490-5 - The role of the sympathetic nervous system on the biological activity of invariant natural killer T lymphocytes
• Grantee: Alexandre de Castro Keller
• Support Opportunities: Regular Research Grants