Acetylcholine polarizes dendritic cells toward a Th2-promoting profile

Area of Science:

• Neuroimmunology
• Cellular immunology

Background:

• The neural and immune systems exhibit reciprocal regulation, with acetylcholine (ACh) modulating immune responses.
• Immune cells, including dendritic cells (DCs), possess a non-neuronal cholinergic system activated during inflammation.
• Previous studies confirmed muscarinic receptors and ACh-metabolizing enzymes in DCs.

Purpose of the Study:

• To investigate the effect of acetylcholine (ACh) on the functional profile of dendritic cells (DCs).
• To determine if ACh influences DC-mediated immune responses, particularly T-helper 2 (Th2) polarization.

Main Methods:

• Dendritic cells (DCs) were generated from monocytes or isolated from peripheral blood (CD1c+).
• Phenotypic analysis, cytokine production (ELISA, intracellular staining), and receptor expression (flow cytometry, qRT-PCR) were assessed.
• Mixed lymphocyte reactions (MLRs) were used to evaluate T cell responses.

Main Results:

• ACh treatment of DCs upregulated OX40L, Th2-chemokines (MDC, TARC), and promoted IL-4, IL-5, IL-13 production by T cells in MLRs.
• TSLP-induced DC activation and T cell cytokine production were further enhanced by co-treatment with ACh.
• ACh boosted TSLP-driven expression of OX40L, HLA-DR, and CD83 on DCs.

Conclusions:

• Acetylcholine (ACh) polarizes dendritic cells (DCs) towards a T-helper 2 (Th2)-promoting profile.
• ACh enhances DC function and cytokine production, influencing adaptive immune responses.