Trends in Neurosciences
ReviewNeuronal Regulation of Immunity in the Skin and Lungs
Section snippets
The Nervous and Immune Systems: Allies Working under Duress
Our barrier tissues are under constant assault from a variety of environmental threats, including noxious chemicals, thermal changes, mechanical injury, and microbial pathogens. The nervous and immune systems are specifically armed to combat these assailants to maintain homeostasis and to coordinate host defense. Mammalian barrier tissues including the skin, lungs, and gut are innervated by the PNS that serves to detect stimuli, including harmful ones, to respond to them, and to regulate
Neuroimmune Interactions at Barrier Tissues
Mammalian barrier tissues (e.g., skin, cornea, respiratory tract, gastrointestinal tract) interface with the environment, and must discern between innocuous and noxious stimuli, as well as maintaining homeostasis and integrity under changing conditions. The immune and nervous systems are tasked to carry out these essential functions. The immune system uses innate and adaptive mechanisms for host defense. The nervous system uses sensory neurons to induce protective nociceptive neural reflexes
Neuroimmune Interactions That Regulate Barrier Function
Barrier functions in the lungs and the skin are important in maintaining homeostasis and preventing infection. In mucosal surfaces such as the lung, CGRP, a neuropeptide from nociceptor neurons, has been found to regulate mucus production, which is a key aspect of barrier function 12., 13.. Nociceptor neurons also mediate barrier leakiness from the lung parenchyma into the blood during bacterial infection [14]. Mechanisms such as tight junction regulation, antimicrobial peptide production,
Neuroimmune Interactions in the Skin
The skin is one of the largest organs in the human body, and its integrity is necessary for homeostasis, protecting barrier function, and combating invading dangers such as pathogens. The nerve fibers innervating the skin are in close proximity to skin structural and functional cells, including keratinocytes, fibroblasts, endothelial cells, Schwann cells, and resident immune cell populations [16]. The cutaneous sensory nerve fibers (CSNFs), which innervate both the dermal and epidermal layers,
Neuroimmune Interactions in the Respiratory Tract
Gas exchange with the external atmosphere occurs in the lungs. During respiration, the lung epithelial surface acts as a barrier surface that comes into direct contact with the environment [46]. With the constant risk of exposure to harmful substances, detection of these potential dangers and pulmonary immunity against them are important. Nerves are therefore crucial in quickly detecting harmful substances to coordinate immune responses, which ultimately can limit the magnitude of lung
Concluding Remarks and Future Perspectives
Barrier tissues including the skin and respiratory tract are constantly exposed to the outside environment as well as to threats to our health and internal homeostasis. These tissues are therefore heavily innervated, and the nervous system is poised to quickly detect insults and in turn recruit the immune system and communicate with it. This establishes crucial neuroimmune crosstalk that is necessary for maintenance of barrier function and host defense. Although there are some shared features
Outstanding Questions
What is the integrative logic of neural control of immunity in barrier surfaces? Although it is well established that both the sensory and autonomic branches of the peripheral nervous system control immunity, the biological advantages for why some peripheral neural signals activate immune responses whereas others suppress them remains unclear. Understanding how neural signals are integrated by the immune system as a whole and within individual cell types is an important future research topic.
Acknowledgments
The laboratory of I.M.C. is funded by National Institutes of Health (NIH) grants F31 AI138384-01A (to K.J.B), NIH/National Center for Complementary and Integrative Health (NCCIH) DP2AT009499 (to I.M.C.), NIH/National Institute of Allergy and Infectious Diseases (NIAID) R01AI130019 (to I.M.C.), and the Chan Zuckerberg Initiative (to I.M.C.). Select images were adapted from Servier Medical Art (www.servier.com).
Glossary
- Antigen-presenting cells (APCs)
- cells that present antigens in complex with MHCs on their surfaces to T cells.
- Bronchoalveolar lavage fluid (BALF)
- the fluid that results from a diagnostic procedure in which cells and other components from bronchial and alveolar spaces are obtained for various studies or diagnoses. BALF is typically analyzed to diagnose lung diseases.
- Dermal dendritic cells (dDCs)
- APCs located in the skin dermal layer, which process and present antigens on their cell surface to T
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2024, Fundamental ResearchCitation Excerpt :It is thus not clear how the neuronal signals may influence inflammation in different contexts, and it is likely that various neural types and their associated neurotransmitters could execute pro- or anti-inflammatory functions in concert with the responsive pancreatic-residential cells or infiltrating immune cells. For instance, most of the spinal afferents, vagal sensory axons, and intrapancreatic neurons express neuropeptides including calcitonin gene-related peptide (CGRP), which affects inflammation in multiple organs such as the lung and gut [1,25,26]. In the lung, CGRP works in concert with intrleukin-33 (IL-33) and neuromedin-U (NMU) and supports IL-5 but constrains IL-13 expression and group 2 innate lymphoid cells (ILC2) proliferation [27].
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