Inflammatory macrophage phenotype in BTBR T+tf/J mice

Area of Science:

• Neuroimmunology
• Behavioral immunology
• Autism Spectrum Disorder research

Background:

• Autism Spectrum Disorder (ASD) is behaviorally defined but often associated with increased pro-inflammatory cytokines.
• The BTBR T+tf/J (BTBR) mouse strain exhibits autism-relevant behaviors like social deficits and repetitive actions.
• This study investigates if BTBR mice share the inflammatory immune profile seen in children with ASD.

Purpose of the Study:

• To characterize the myeloid immune profile of BTBR mice.
• To investigate the association between immune profiles and autism-relevant behaviors in BTBR mice.
• To compare the inflammatory response of BTBR mice to the C57BL/6J (C57) control strain.

Main Methods:

• Assessed social interest and repetitive self-grooming in BTBR and C57 mice.
• Measured cytokine production from bone-marrow derived macrophages stimulated with LPS, IL-4/LPS, or IFNγ/LPS.
• Analyzed M1/M2 macrophage polarization markers and cytokine levels.

Main Results:

• BTBR macrophages showed higher IL-6, MCP-1, MIP-1α, and lower IL-10 after LPS stimulation, indicating an exaggerated inflammatory profile.
• BTBR macrophages exhibited impaired M2 polarization (less IL-10, more IL-12p40) after IL-4/LPS.
• Enhanced M1 polarization (higher IL-12(p70)) was observed in BTBR macrophages after IFNγ/LPS stimulation.
• Repetitive grooming frequency positively correlated with IL-12(p40), IL-12p70, IL-6, and TNFα production.

Conclusions:

• BTBR mice display a pro-inflammatory, M1-skewed macrophage profile compared to C57 mice.
• This heightened inflammation is linked to repetitive grooming behavior in BTBR mice.
• The findings suggest a potential role for neuroinflammation in the repetitive behaviors associated with autism.