Autism spectrum disorders and natural killer cells: a review on pathogenesis and treatment

ABSTRACT

Introduction: Autism spectrum disorder (ASD), as a wide spectrum of neurodevelopmental disorders, is characterized by early-onset impairments in social-communication, repetitive behaviors, and restrictive interests.

Areas covered: Although still unknown, there are some pieces of evidence suggesting altered immune function in the etiology of ASD. This review aims to summarize studies linking Natural Killer (NK) cells to ASD by searching through databases like MEDLINE and Scopus up to October 2020. NK cells play important roles in the innate immune system and immune regulation. As parts of the immune system, they interact with the neural system as well. Immune dysregulations such as autoimmunity and improper immune responses to both internal and external stimulations, especially in early developmental stages of the brain, may induce neurodevelopmental disorders. NK cells’ dysfunction in children with ASD as well as their parents have been highlighted in many studies.

Expert opinion: Changes in the frequency, gene expressions, cytotoxicity features, and receptors of NK cells are reported in children with ASD. Immune therapy for children with ASD with immune abnormality has shown promising results. However, further studies are needed to elucidate the exact role of NK cells in the pathogenesis of ASD providing future treatment options for these children.

KEYWORDS:

• Immune system
• genetics
• immune therapy
• killer cell immunoglobulin-like receptors
• human leukocyte antigen

Article highlights

• Reduced efficacy of NK cells to deal with stimuli in ASD children despite increased cytotoxicity and frequency of them in unstimulated condition.

• Upregulation of some genes related to NK cells in ASD children.

• Altered receptors and ligands on NK cells including KIR and HLA in ASD children and their parents especially mothers.

• Effectiveness of immune-therapy in ASD children with abnormality in immune system.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.