Single-cell profiling reveals GPCR heterogeneity and functional patterning during neuroinflammation.

Area of Science:

• Immunology
• Neuroscience
• Cell Biology

Background:

• G protein-coupled receptor (GPCR) expression is crucial for cellular function.
• Previous studies focused on bulk cell populations, limiting understanding of individual cell GPCR heterogeneity.
• Limited data exists on GPCR expression in individual immune and endothelial cells during neuroinflammation.

Purpose of the Study:

• To investigate single-cell GPCR expression in primary T cells, myeloid cells, and endothelial cells.
• To analyze GPCR expression changes under naive conditions and during experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis.
• To identify functionally relevant cell subgroups with distinct GPCR profiles during neuroinflammation.

Main Methods:

• Microfluidic-based single-cell analysis of GPCR expression.
• Analysis of primary T cells, myeloid cells, and endothelial cells.
• Comparison of GPCR expression in naive conditions versus EAE.

Main Results:

• Neuroinflammation significantly alters GPCR heterogeneity and patterning in single cells.
• Identification of distinct subgroups within spinal cord-infiltrating CD4 T cells, macrophages, microglia, and endothelial cells based on GPCR profiles.
• Demonstration of therapeutic potential using GPCRs CXCR4, S1P1, and LPHN2 for modulating Th17 cells and endothelial cells.

Conclusions:

• Single-cell GPCR expression analysis is effective in identifying functionally relevant subpopulations.
• Specific GPCR repertoires define distinct cell subgroups during neuroinflammation.
• This approach provides a foundation for developing novel therapeutic strategies for immune disorders.