Dopaminergic modulation of NK cell maturation and immune-associated social behavior in a 15q dup mouse model.

Dopaminergic modulation of NK cell maturation and immune-associated social behavior in a 15q dup mouse model.

Publication date: Jul 01, 2026

Autism spectrum disorder (ASD) is a neurodevelopmental condition frequently associated with immune dysregulation, yet the mechanistic basis of this comorbidity remains poorly understood. Using the paternal 15q11-13 duplication (15q dup) mouse model of ASD, we identify that systemic dopamine deficiency is associated with impaired terminal maturation and effector function of natural killer (NK) cells. Functionally, dopaminergic stimulation promotes NK cell maturation and activity in a D1-like receptor-cAMP associated manner, accompanied by altered expression of the NK maturation-related transcription factor Tbx21. Notably, pharmacological activation of D1-like receptors enhances anti-tumor immunity and improves social behavior in an NK-dependent manner in 15q dup mice. Together, these findings support a dopaminergic neuroimmune framework in which systemic dopamine signaling is associated with innate immune regulation and immune-dependent behavioral phenotypes in the 15q dup mice.

Concepts Keywords
Autism Animals
Killer Autism Spectrum Disorder
Mice Autism spectrum disorder
Pharmacological Chromosomes, Human, Pair 15
Tbx21 D1-like receptor
Disease Models, Animal
Dopamine
Dopamine
Dopamine
Killer Cells, Natural
Male
Mice
NK cells
Receptors, Dopamine D1
Receptors, Dopamine D1
Social Behavior

Semantics

Type Source Name
disease MESH Autism spectrum disorder
drug DRUGBANK Dopamine
drug DRUGBANK Cyclic Adenosine Monophosphate
disease MESH tumor
disease MESH Disease Models Animal

Original Article

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