Source: Australian National University.

The Australian National University (ANU) has led the discovery of brain-like activity in the immune system that promises better treatments for lymphoma, autoimmune diseases and immunodeficiency disorders, which collectively affect millions of people globally.

Lead researcher Ilenia Papa from ANU said the research confirmed for the first time that human immune cells contain particles that have neurotransmitters including dopamine, which plays a crucial role in immune responses.

“These particles were previously thought to only exist in neurons in the brain and we think they are, potentially, an excellent target for therapies to speed up or dampen the body’s immune response, depending on the disease you’re dealing with,” said Ms Papa, a PhD scholar at The John Curtin School of Medical Research (JCSMR), ANU.

Neurons rely on synaptic interactions and neurotransmitters such as dopamine, which are small molecules transmitted across synapses to deliver signals from one cell to another that play a major role in reward-motivated behaviour.

“Like neurons, specialised T cells transfer dopamine to B cells that provides additional ‘motivation’ for B cells to produce the best antibodies they can to help to clear up an infection,” Ms Papa said.

“The human body has developed an advanced form of protection against bacteria, viruses and other foreign bodies that relies on the immune system.

“Immune responses are essential for recognising and defending humans against substances that appear foreign and harmful to the individual.”

The research, published in Nature, involved a collaboration with members of a Human Frontier Science Program consortium from the United Kingdom, the United States and Germany, and with other researchers in Italy.

Co-researcher Professor Carola Vinuesa from JCSMR said the new findings opened the door to using available drugs to improve therapies for lymphoma, autoimmunity and immunodeficiency disorders.

“We hope to use these findings to make the immune response to vaccines and infections faster and more productive, and slower and less active for autoimmune conditions where the body attacks itself,” Professor Vinuesa said.

The researchers analysed around 200 tissue samples from children who had their tonsils removed, observing the transfer of dopamine from specialised T cells to B cells through a synaptic interaction.

They also worked with a mathematician to model the immune system’s brain-like activity in a human in response to vaccines.

Source: Kate Prestt – Australian National University
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Abstract for “TFH-derived dopamine accelerates productive synapses in germinal centres” by Ilenia Papa, David Saliba, Maurilio Ponzoni, Sonia Bustamante, Pablo F. Canete, Paula Gonzalez-Figueroa, Hayley A. McNamara, Salvatore Valvo, Michele Grimbaldeston, Rebecca A. Sweet, Harpreet Vohra, Ian A. Cockburn, Michael Meyer-Hermann, Michael L. Dustin, Claudio Doglioni & Carola G. Vinuesa in Nature. Published online July 12 2017 doi:10.1038/nature23013

Abstract

TFH-derived dopamine accelerates productive synapses in germinal centres

Protective high-affinity antibody responses depend on competitive selection of B cells carrying somatically mutated B-cell receptors by follicular helper T (TFH) cells in germinal centres. The rapid T–B-cell interactions that occur during this process are reminiscent of neural synaptic transmission pathways. Here we show that a proportion of human TFH cells contain dense-core granules marked by chromogranin B, which are normally found in neuronal presynaptic terminals storing catecholamines such as dopamine. TFH cells produce high amounts of dopamine and release it upon cognate interaction with B cells. Dopamine causes rapid translocation of intracellular ICOSL (inducible T-cell co-stimulator ligand, also known as ICOSLG) to the B-cell surface, which enhances accumulation of CD40L and chromogranin B granules at the human TFH cell synapse and increases the synapse area. Mathematical modelling suggests that faster dopamine-induced T–B-cell interactions increase total germinal centre output and accelerate it by days. Delivery of neurotransmitters across the T–B-cell synapse may be advantageous in the face of infection.

“TFH-derived dopamine accelerates productive synapses in germinal centres” by Ilenia Papa, David Saliba, Maurilio Ponzoni, Sonia Bustamante, Pablo F. Canete, Paula Gonzalez-Figueroa, Hayley A. McNamara, Salvatore Valvo, Michele Grimbaldeston, Rebecca A. Sweet, Harpreet Vohra, Ian A. Cockburn, Michael Meyer-Hermann, Michael L. Dustin, Claudio Doglioni & Carola G. Vinuesa in Nature. Published online July 12 2017 doi:10.1038/nature23013