Cell . . . Important advances in neuroimmune - Skin TRPV1 neurons activate type 17 to prevent the immune system.

My best friend, old Red Riding Hood, wrote an article in the book of songs, which said, "Xiangsha has skin" (Note: only literal meaning).as the main defense organ of the body, the skin plays an important role in perceiving the changes of cold and hot outside, feeling the pressure and pain, resisting the invasion of bacteria and viruses and so on.so, how does the skin function? It is generally believed that in addition to epidermal cells, there are two types of cells on the skin: one is neurons, which can stretch out nerve endings like tentacles, which can spread throughout the skin. Some of these tentacles sense temperature and some feel pressure, while neurons expressing TRPV1 specifically sense physical pain and transmit the pain sensation to the spine and brain [1]; the other is immune cells When there are external bacteria and viruses invading or their own diseases occur, they quickly gather and release cytokines to resist foreign enemies. At the same time, they will record the information and coping styles of the enemy. Next time there is the same enemy, the skin can respond more quickly and effectively, which is called "preventive immunity" [2].so, is there a relationship between neurons and immune cells? Recently, Daniel h. Kaplan of the University of Pittsburgh published an article on cell, which showed that neurons under skin can trigger type 17 immune response of immune cells.the researchers implanted photosensitive elements into the mouse TRPV1 neurons, and the laser irradiates specific skin areas, and the neurons in this area are activated.the authors found that the ears of mice had inflammatory symptoms such as redness and swelling. That is to say, in the absence of any trauma or bacterial invasion, the activation of TRPV1 neurons alone is enough to activate the immune system.next, the author wants to know which part of the immune system is activated.by means of tissue staining and microscopy, the authors found that a large number of immune cells were collected to the irradiation area after laser irradiation.by flow cytometry, these cells were mainly γ δ T cells, CD4 + T cells and neutrophils, which were the markers of type 17 immune activation.type 17 immunity, specifically refers to the activation of immune cells that can secrete interleukin-17 (IL-17).next, the authors further confirmed that the γ δ T cells and CD4 + T cells in the irradiation area did secrete a large amount of IL-17.at the same time, the inflammation caused by the activation of TRPV1 neurons in ear skin was greatly reduced by intraperitoneal injection of IL-17 antibody to mice.these results suggest that TRPV1 neurons are activated enough to activate type 17 immune response.so, the next question is, how do neurons activate type 17 immunity? Neurons usually act by releasing neurotransmitters, and CGRP (calcitonin gene related peptide) is the main neurotransmitter released by TRPV1 neurons.the authors found that a large amount of CGRP was released from neurons in the spinal cord and ear of mice after laser irradiation.at the same time, the activation of type 17 immunity was significantly reduced in mice injected with CGRP antagonist.in conclusion, after TRPV1 neurons are activated, a large amount of neurotransmitter CGRP is released. Next, CGRP recruits immune cells, induces IL-17 secretion, and starts type 17 immunity. finally, the author wants to know whether the type 17 inflammation caused by TRPV1 neuronal activation has any effect on other parts of the body? The authors found that the blood flow was more intense, the neurons became active and the secretion of CGRP increased in the area near the irradiation area of mouse ears, and then type 17 immunity was activated. how is this reaction caused? Bupivacaine, a sodium channel inhibitor, was introduced to inhibit the transmission of information from neurons to other neurons through the reflex arc. the authors found that in mice injected with the drug, the activation of TRPV1 neurons, CGRP release and type 17 inflammatory response were significantly reduced in the irradiated area. That is to say, as shown in the figure below, TRPV1 neurons in the stimulated area activated and released CGRP to initiate type 17 immune response. Meanwhile, the activated neurons could pass through the reflex arc, TRPV1 neurons were activated and type 17 immune response was activated. this "preventive" activation can resist foreign invasion faster and better, and has a very positive significance for the body. the organism is organic and orderly, and moves the whole body by pulling one hair; each system influences and regulates each other, complements each other, and performs its mission more quickly, better and less. the interaction between the nervous system and the immune system is one of the hotspots in biological research. the authors focused their attention on the skin, an important defense organ, and found that TRPV1 neurons can effectively activate type 17 immune response in the activated and adjacent regions. of course, there are still many problems to be solved. For example, after the initiation of type 17 immune response, many immune cells gather and release many cytokines, including IL-17, and the skin microenvironment changes. What impact will this have on neurons or nervous system itself, as well as other skin cells, such as epithelial cells? For another example, after TRPV1 neurons are activated, they transmit information to the spine and brain through the reflex arc. How does the spine and brain react? For example, the author's work is basically completed by mice in normal physiological state. How do neurons and type 17 immunity respond to pathological conditions, such as trauma, bacterial invasion, skin disease and lupus erythematosus and other autoimmune diseases? Does the cutaneous nervous system still activate the immune system? How to start? In a word, there are many and interesting problems in the field of neuroimmunology. If we can solve one or two problems, we can have a better understanding of the body and more accurately and effectively solve the major problems of human survival and development. original link: plate maker: Ke, Ref. 1. Julius, D., and BASBAUM, A.I. (2001). Molecular mechanisms of nociception. Nature 413, 203 – 210.2. Kashem, S.W., and Kaplan, D.H. (2016). Skin immunity to Candida albicans. Trends immune. 37, 440 – 450