Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 149, Issue 6, Pages 1875-1898Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2022.03.010
Keywords
Atopic eczema; pruritus; itch; pathophysiology; eczema; cytokine; neuropeptide; neuroimmunology; therapy
Categories
Funding
- National Priorities Research Program of the Qatar National Research Fund of Qatar Foundation [NPRP11S-0117-180326]
- Internal Research Grand Competition of the MRC Fund, Hamad Medical Corporation, Qatar [IRGC-04-SI-17-151, IRGC-07-JI-20-725]
Ask authors/readers for more resources
Atopic dermatitis is a common chronic inflammatory skin disease, and its pathogenesis involves the dysregulation of neuroimmune circuits. Abnormal neuroimmune circuits can lead to inflammation, pruritus, pain, and skin barrier dysfunction. Understanding neuroimmune circuits and neuronal signaling is crucial for controlling the pathological mechanisms of atopic dermatitis.
Atopic dermatitis (AD) is a common, chronic-relapsing inflammatory skin disease with significant disease burden. Genetic and environmental trigger factors contribute to AD, activating 2 of our largest organs, the nervous system and the immune system. Dysregulation of neuroimmune circuits plays a key role in the pathophysiology of AD, causing inflammation, pruritus, pain, and barrier dysfunction. Sensory nerves can be activated by environmental or endogenous trigger factors, transmitting itch stimuli to the brain. On stimulation, sensory nerve endings also release neuromediators into the skin, contributing again to inflammation, barrier dysfunction, and itch. In addition, dysfunctional peripheral and central neuronal structures contribute to neuroinflammation, sensitization, nerve elongation, and neuropathic itch, thus chronification and therapy resistance. Consequently, neuroimmune circuits in skin and central nervous system may be targets to treat pruritus in AD. Cytokines, chemokines, proteases, lipids, opioids, and ions excite/sensitize sensory nerve endings, which not only induces itch but further aggravates/perpetuates inflammation, skin barrier disruption, and pruritus as well. Thus, targeted therapies for neuroimmune circuits as well as pathway inhibitors (eg, kinase inhibitors) may be beneficial to control pruritus in AD either in systemic and/or in topical form. Understanding neuroimmune circuits and neuronal signaling will optimize our approach to control all pathological mechanisms in AD, inflammation, barrier dysfunction, and pruritus.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available