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Analysis of invariant natural killer T lymphocytes spectrum in autism

Abstract

A growing body of evidence supports the existence of a close relationship between the immune system (IS) and the pathogenesis of autism spectrum disorder (ASD). Besides the genetic predisposition, environmental agents such as valproic acid and infectious diseases represent a risk factor for ASD. Although the mechanisms involved in this phenomenon remain to be clarified, experimental models demonstrated a correlation between pro-inflammatory cytokines and ASD-like phenotype in the offspring. In parallel, individuals with ASD are affected by immune disorders such as autoimmunity and susceptibility to infectious diseases. Thus, ASD development is associated with a pro-inflammatory state during gestation that compromises both the brain development and the future homeostasis of the IS. In this context, the role of invariant Natural Killer T (iNKT) lymphocytes in ASD development remains to be determined. The iNKT cells are non-conventional lymphocytes with the ability to rapidly produce several cytokines and thereby modulate numerous immune-mediated diseases. For example, they have key roles in the homeostasis of decidual immune cells, abortion, and both pre and late-term pregnancy. Also, ASD patients exhibit a significant reduction in iNKT frequency in blood, similar to those observed in the BTBR genetic model of ASD. Therefore, there is mounting evidence pointing towards an important role of iNKT cells in the ASD pathophysiology. To address this hypothesis, we will take advantage of a murine model of valproic acid-induced ASD and J±18-/- mice, which lack iNKT cells. Thus, this proposal aims to promote the association between the Laboratory of Experimental Immunopathology (Brazil) and the Laboratory of Neuroimmunology and Behavioral Research (UK) to determine the relationship between iNKT lymphocytes and ASD pathophysiology for the future development of conjoined projects to improve the knowledge and management of ASD. In addition, the expertise and technology exchange will increase the comprehension of the relationship between the iNKT lymphocytes and the nervous system, and improve the development of new approaches for immunotherapy. (AU)

Articles published in Agência FAPESP Newsletter about the research grant: