Attila Szabo is a Postdoctoral Fellow at the Norwegian Centre for Mental Disorders Research (NORMENT), University of Oslo, Norway. He holds two Master’s degrees in Molecular biology, Biochemistry (MSc) and in Philosophy (MA), both from the University of Debrecen, Hungary. He received his PhD degree in Biomedicine with a focus on cellular and molecular immunology. His research interest involves the biology of inflammation, neuroimmunology, neuropharmacology, and biological psychiatry. He is also interested in the philosophical questions of mind-body interaction, and the phenomenology of altered states of consciousness. His current research focuses on serotonin and sigma receptors, their modulatory role in immune responses and cellular functions. In this context, he is specifically interested in the regulatory potential of dimethyltryptamine (DMT) and its analogues (e.g. 5-MeO-DMT and bufotenin) on human immune cell, neuron, and glia functions under various physiological conditions.
“The serotonin receptor 5-HT2B is a potent immunomodulator in human dendritic cells”
Serotonin is a monoamine neurotransmitter that signals through a wide array of receptors (5-HT1-7) many of which are also involved in immune processes. Dendritic cells (DCs) are crucial players in immune defense by orchestrating immune responses via their vast repertoire of pattern recognition receptors and antigen-presenting capability. Although serotonin is known to influence immunity at many levels, cell type-specific expression and function of its receptors remains poorly understood. Furthermore, serotonergic psychedelics, such as DMT, LSD, and psilocin show agonistic activity mainly at the 5-HT1 and 5-HT2 sites. Here we aimed to study serotonin receptor expression and function in human DCs. We found that the 5-HT2B receptor-subtype is solely expressed by an inflammatory DC subset. Specific 5-HT2B activation potently inhibited proinflammatory cytokine and chemokine (TNF-α, IL-6, IL-8, IP-10, IL-12) production. 5-HT2B agonism also interfered with the polarization of moDC-primed helper T cells towards inflammatory Th1 and Th17 effector lymphocytes. Our results expand the biological role of 5-HT2B which may act not only as a neurotransmitter receptor, but also as an important modulator of both innate and adaptive immunity. These findings also raise the possibility of harnessing the biological activity of serotonergic psychedelics at 5-HT2B in the treatment of various inflammatory and autoimmune conditions.