Sophie Ugolini has been working for many years in her laboratory at the Marseille-Luminy Immunology Center on the interactions that exist between the nervous system and the immune system. “Each of these fields is conventionally studied by researchers of a different specialty. However, when one is injured, sensory neurons specializing in pain are immediately activated, but the sentinels of the immune system are also activated to deal with possible pathogens. This research is based on studying the links and the way in which these two systems will eventually communicate with each other at the time of the injury “, she explains. His work, published in the journal Nature in May 2021 and highlighted in another article of the journal Nature Reviews Immunology, led to the identification of a protein involved in this dialogue.
Neurons that regulate the immune system
This protein, called TAFA4, is secreted by certain sensory neurons in the skin which are activated during skin inflammation caused by overexposure to ultraviolet rays, in other words during sunburn. These neurons are responsible for transmitting the pain signal, but they also help regulate the immune response. Thus, in mice deprived of these cells which innervate the skin, the inflammation persists for a longer time and healing is more difficult. “TAFA4 acts on cells of the immune system called pro-repair macrophages which play an important role in the control of inflammation and repair processes “ explains Sophie Ugolini. They do this through another protein, interleukin 10 (IL-10), which has anti-inflammatory action. TAFA4 stimulates the production of IL-10 and promotes the survival of the macrophages that produce it.
These neurons which produce TAFA4 are those specialized in the perception of caresses or touches of the skin. Does this mean that caresses can promote healing or locally limit its inflammation? “It is not possible to answer this question at the moment. In fact, the TAFA4 protein assay had never been performed before and we have developed a test specifically for this study to quantify it in tissues. The production of TAFA4 has not yet been studied in the case of caresses, as has its physiological role in humans. This is one of our research axes current “answers the researcher.
Sophie Ugolini. Credit SU.
New therapeutic avenues
The other line of research will consist of studying the therapeutic potential of TAFA4. Indeed, the macrophages on which the protein acts are present in practically all tissues: in a waking state, they are ready to react to an attack on the organism. And if there is inflammation, others can be recruited that come from the blood and produce inflammatory cytokines. “We show that TAFA4 decreases the production of these cytokines which are found in many inflammatory pathologies, including in severe forms of Covid-19 and in other autoimmune diseases”Emphasizes the immunity specialist. A track that is being evaluated pre-clinical at Luminy where the action of the molecule is tested on several disease models such as rheumatoid arthritis or psoriasis, a dermatological condition.
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The discovery of this regulatory function of the immune system by the sensory system of the skin was confirmed in another study conducted by the same team. These results, published in the journal Nature Communications, relate to lesions caused by HSV1, the virus responsible for cold sores. If the protocol is different and involves a larger proportion of sensory neurons, the results again indicate that the nervous system contributes to the resolution of lesions and the fight against infection. “Neuro-immunology is a growing discipline which will open up new therapeutic avenues for us and will also allow us to better understand the functioning of the organism in the face of infections or physical or chemical attacks “ Sophie Ugolini concludes.