Complex environmental cues have profound effects on human health and diseases. Whether immune disorders such as asthma are sensitive to environmental factors, especially solar ultraviolet (UV) radiation, remains to be investigated. Many studies have described the regulatory effects of UVB (290–315 nm) irradiation on experimental allergic disease in mice. However, the mechanisms of UVB radiation-induced immune suppression remain debated.
Asthma is a common chronic pulmonary inflammatory disease that affects more than 300 million people worldwide6. Emerging evidence has demonstrated that in addition to CD4+ Th2 cells, group 2 innate lymphoid cells (ILC2s) are an important and much earlier source of type 2 cytokines, such as IL-5, IL-13, AREG, and IL-4. Upon different initial triggers, such as protease allergens, fungi, and viruses, lung epithelial cells secrete IL-33, IL-25, and thymic stromal lymphopoietin (TSLP), which activate ILC2s to induce robust production of IL-5 and IL-13 to favor the induction of a type 2 immune response. These cascades drive eosinophil infiltration, airway hyperresponsiveness (AHR), and mucus production. In addition to alarmins, cytokines, lipid mediators, neurotransmitters, hormones, and nutrients have been shown to regulate ILC2 function. These factors cooperatively make ILC2s highly sensitive in the tissue microenvironment. The central nervous system (CNS)-mediated release of circulating mediators, such as endogenous opioids and a diverse range of other hormones, can also affect innate and adaptive immune cells. As the “conductor of the endocrine orchestra”, the hypothalamic-pituitary (HP) unit has been reported to produce hormones such as prolactin (PRL), adrenocorticotropic hormone (ACTH) and thyroid stimulating hormone (TSH) to regulate immune responses. Moreover, some environmental factors, such as UV radiation, can activate the HP unit and release downstream hormones, suggesting that environmental stress and the neuroendocrine system might modulate the immune responses. Although considerable advances have been made in defining different factors that regulate ILC2 responses, the detailed mechanisms underlying the regulation of ILC2s and type 2 inflammation by environment-driven neuroendocrine in airway inflammation remain defined.
The researchers analyzed asthma emergency department (ED) visit distribution data for 17,818 individuals from 2015-2019 in Shanghai, China. They found that asthma attacks were significantly associated with solar UVB radiation and its seasonal fluctuation, resulting in a lower incidence of asthma during the summer. Similar results were obtained by analyzing public data from the Centers for Disease Control and Prevention (CDC) and Climate Prediction Center websites from USA. It was evident that exposure of the eyes to UVB radiation upregulated Pomc expression in the pituitary gland. Then, an increased α-MSH level in the serum was detected and found to protect mice from allergic airway inflammation by reducing the function of ILC2s via the α-MSH receptor subtype Mc5r. A mechanistic study revealed that the α-MSH–MC5R axis inhibited IL-7R-STAT and NF-κB pathways in activated pulmonary ILC2s, as evidenced by the downregulation of and STAT3/5 and p65 phosphorylation. The therapeutic effects of α-MSH were validated with clinical data and mouse models of house dust mite (HDM)- and ovalbumin (OVA)-alum-induced chronic inflammation. The researchers also noted that plasma α-MSH concentrations were negatively correlated with the number and function of ILC2s among peripheral blood mononuclear cells (PBMCs) in asthmatic patients. These findings provide insights into the role of neuroendocrine α-MSH in targeting ILC2s to limit lung inflammation and provide a new option for controlling allergic lung inflammation. The study also provides some scientific evidence to support century-old anecdotal reports that beach and mountain resort holidays associated with increased UV exposure through sunlight are beneficial in lung inflammation treatment. The study has been published on Nature Communications online of September 12, 2023.
Contact: bsun@sibs.ac.cn
Reference: https://www.nature.com/articles/s41467-023-41319-1
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