The role of the sympathetic nervous system on the biological activity of invariant natural killer T lymphocytes

• Grant number: 19/11490-5
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2019
• End date: January 31, 2022
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Alexandre de Castro Keller
• Grantee: Alexandre de Castro Keller
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Alexandre Salgado Basso ; Antonio Mauro Rezende ; Daniella Arêas Mendes da Cruz ; Roberto Rudge de Moraes Barros
• Associated research grant(s): 19/23427-6 - Analysis of invariant natural killer T lymphocytes spectrum in autism, AP.R SPRINT

Abstract

Although a growing body of evidence supports the notion that the sympathetic nervous system (SNS) influences the immune system (IS), the relationship between the SNS and the invariant Natural Killer T lymphocytes remains underestimated. These cells are part of a lymphocyte population with selectivity for lipid antigens that are recognized by their potent immunoregulatory properties. Upon activation by their principal agonist, ±-galactosylceramide (±-GC), they rapidly produce polarizing cytokines, such as IFN-³ and IL-4, an ability exploited as immunotherapy against cancer. Despite promising results, the outcome of the clinical trials remains underwhelming. Because several studies focused in the development of more potent agonists or in carriers systems that increase their biological activity, other approaches, such as the modulation of the microenvironment surrounding iNKT cells during their activation remains neglected. Because of the influence of SNS on several cellular reactions, we hypothesize that in response to iNKT activation or stress conditions, such as cancer, the SNS modulates the biological activity of iNKT lymphocytes by secreting catecholamines, as norepinephrine (NE). This notion finds support in pieces of evidence from literature, and preliminary results from our group showing a unique expression pattern of adrenergic receptors in thymic iNKT cells and the impact of NE secretion in their ontogeny and distribution in the periphery.Thus, understanding the relationship between the SNS and iNKT lymphocytes may improve the development of new strategies to iNKT-based immunotherapy. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

GIL, NOEMI L.; AZEVEDO, GABRIELA A.; BALBINO, ALEKSANDRO M.; SILVA, MARINA M.; CARVALHO, MARIA HELENA C.; AKAMINE, ELIANA H.; KELLER, ALEXANDRE C.; LANDGRAF, RICHARDT G.; LANDGRAF, MARISTELLA A.. Intrauterine growth restriction leads to a high-corticosterone producing offspring: An implication for pulmonary infection susceptibility. Life Sciences, v. 281, SEP 15 2021. (19/11490-5)

FERNANDES, EDGAR RUZ; BARBOSA, MARCELA LUIZE; AMARAL, MARCELO PIRES; APOSTOLICO, JULIANA DE SOUZA; SULCZEWSKI, FERNANDO BANDEIRA; TUFIK, SERGIO; ANDERSEN, MONICA LEVY; BOSCARDIN, SILVIA BEATRIZ; KELLER, ALEXANDRE CASTRO; ROSA, DANIELA SANTORO. Sleep Disturbance during Infection Compromises Tfh Differentiation and Impacts Host Immunity. ISCIENCE, v. 23, n. 10, OCT 23 2020. (19/11490-5, 17/17471-7)

SOUSA, MARIA E. P.; GONZATTI, MICHELANGELO B.; FERNANDES, EDGAR R.; FREIRE, BEATRIZ M.; GUERESCHI, MARCIA G.; BASSO, ALEXANDRE S.; ANDERSEN, MONICA L.; ROSA, DANIELA S.; KELLER, ALEXANDRE C.. Invariant Natural Killer T cells resilience to paradoxical sleep deprivation-associated stress. BRAIN BEHAVIOR AND IMMUNITY, v. 90, p. 208-215, NOV 2020. (17/17471-7, 19/11490-5)